Cystic Fibrosis is caused by defects in the CFTR gene. The gene encodes for the protein cystic fibrosis transmembrane conductance regulator, which is involved in chloride ion transport and hence mucus production. Sufferers have breathing difficulties, due to sticky mucus buildup in the lungs. They also have severe digestive problems, since pancreatic enzymes are blocked from entering the small intestine, the main locus of nutrient absorption. Male sufferers are normally infertile, due to the lack of functioning vas deferens tubes which lead to the urethra. Diabetes and liver disease are common complications that often develop over time. The mean projected survival time for children born with the condition in the USA in 2010 was estimated at 37 years for women and 40 years for men. The inheritance of the defective gene is autosomal recessive, typically requiring both parents to be asymptomatic carriers of the mutated gene. The condition is relatively common among Caucasian Americans, with an incidence of about 1 in 2,500 to 1 in 3,500. The figures are about 1 in 4,000 to 10,000 for Hispanic Americans, 1 in 15,000 to 20,000 for African Americans, and 1 in 100,000 for Asian Americans. It is estimated that 1 in 29 Caucasian Americans carry the defective gene asymptomatically. The figures are 1 in 46 for Hispanic Americans, 1 in 65 for African Americans, and 1 in 90 for Asian Americans.

Sources

Cystic Fibrosis Foundation, Carrier Testing for CF.

See http://www.cff.org/AboutCF/Testing/Genetics/GeneticCarrierTest/

MacKenzie, T. et al. (2014), “Longevity of Patients with Cystic Fibrosis in 2000 to 2010 and Beyond: Survival Analysis of the Cystic Fibrosis Foundation Patient Registry,”

Annals of Internal Medicine, 161, 233-241.

NIH, Genetics Home Reference: Cystic Fibrosis.

See http://ghr.nlm.nih.gov/condition/cystic-fibrosis

Spinal muscular atrophy (SMA) can be caused by mutations in a number of genes. One of these is the SMN1 gene, which encodes for the spinal motor neuron protein. This protein is required for the maintenance of motor neurons in the spinal cord and brainstem. SMA is divided into different types: types 1-4 of SMA are all caused by mutations of the SMN1 gene, and all involve muscle weakness. Type 1 SMA first occurs before 6 months. Affected babies are unable to hold their heads up or sit up; they typically have difficulty swallowing and breathing, so they tend not to survive beyond the age of two. Type 2 SMA first occurs between 6 months and a year. Babies can sit up, but do not go on to stand or walk unaided in the usual manner. Type 3 SMA first occurs in older children. They can normally walk unaided, but may find climbing stairs or other similar tasks difficult. They may need to use a wheelchair by mid-life. Type 4 SMA first occurs in adulthood. Sufferers have some muscle weakness, tremors, and mild breathing problems. The incidence of all types of spinal muscular atrophy is around 1 in 6,000 to 1 in 10,000 births. It is estimated that around 1 in 40 to 1 in 50 people is a carrier. Although the incidence varies somewhat from country to country, it does not seem to be highly present in any ethnic group. The faulty gene is transmitted in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers.

Sources

NIH, Genetics Home Reference: SMN1 gene.

See http://ghr.nlm.nih.gov/gene/SMN1

NIH, Genetics Home Reference: Spinal Muscular Atrophy.

See http://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy

Prior, T.W. & Russman, B.S., (2000), “Spinal Muscular Atrophy,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1352/

Recombine Website. Spinal Muscular Atrophy: SMN1 linked.

See https://recombine.com/diseases/spinal-muscular-atrophy-smn1-linked

Marfan syndrome is caused by mutations in the FBN1 gene. These lead to abnormalities in the protein fibrillin, which is an essential component of connective tissues. The severity of the symptoms differs widely between different individuals with the defective gene. The syndrome often leads to eye defects, such as lens displacement and myopia. There is an increased risk of retinal detachment, glaucoma, and cataracts. Cardiovascular defects, such as an enlarged aorta and heart valve problems, are common, and can be life threatening. Medication, typically beta blockers, or surgery may be needed to reduce the risk of serious heart failure. Musculoskeletal disorders often occur: these include loose joints, protrusion or indentation of the sternum, and curvature of the spine. Those with the syndrome tend to be unusually tall and thin. Among the general population the risk of having Marfan’s syndrome is about 1 in 5,000, although a parent with the syndrome has a 50:50 risk of their child inheriting the faulty copy of the gene, due to its nature as an autosomal dominant disorder. The disease seems to be spread evenly among all ethnic groups.

Sources

NIH, Genetics Home Reference: Marfan Syndrome. See http://ghr.nlm.nih.gov/condition/marfan-syndrome

National Center for Biotechnology: Marfan Syndrome. See http://www.ncbi.nlm.nih.gov/books/NBK1335/on go to app settings and press "Manage Questions" button.

PreventTest detects mutations (defects in the genes) that are linked to many of the most common cancers. These mutations can unknowlingly be passed from parent to child. PrevenTest screening is for patients with and without cancer. For patients with cancer, it can tell you more about your cancer and the options you have for treatment. For patients without cancer, it can inform you of your potential risks.

Niemann-Pick Disease Type C1 is caused by mutations in the NPC1 gene. This gene is involved in producing a protein involved in the transportation of lipids, including cholesterol. Mutations in the NPC2 gene cause similar effects (Type C2). Symptoms of Niemann Pick C1 typically develop in early childhood, but can first appear in adults. Muscle weakness and ataxia (poor control of movements, etc.) become gradually apparent, along with liver disease, seizures (in some cases), and progressive mental deterioration. Patients are often unable to move their eyes vertically (vertical supranuclear gaze palsy). Swallowing and speech deteriorate progressively, leading to a complete inability to ingest food. Respiratory failure may also occur. Most patients die in their 20’s or 30’s. When the disease first appears in adulthood, psychiatric symptoms tend to predominate. The total incidence of Niemann-Pick disease Type C is around 1 in 120,000 births. About 90% are due to the NPC1 gene. The disease is more common in some ethnic groups, such as Hispanics whose ancestors lived in the upper Rio Grande valley. The defective genes are inherited in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers.

Sources

Millat, G. et al, (1999), “Niemann-Pick C1 disease: the I1061T substitution is a frequent mutant allele in patients of Western European descent and correlates with a classic juvenile phenotype,” American Journal of Human Genetics, 65, 1321-1329.

See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1288284/

NIH, Genetics Home Reference: NCP1 gene.

See http://ghr.nlm.nih.gov/gene/NPC1

NIH, Genetics Home Reference: Niemann-Pick Disease.

See http://ghr.nlm.nih.gov/condition/niemann-pick-disease

Patterson, M. (2000), “Niemann-Pick Disease Type C,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1296/

Recombine Website: Niemann-Pick Disease Type C1.

See https://recombine.com/diseases/niemann-pick-disease-type-c1

Long QT Syndrome 5 (KCNE1) Long QT syndrome 5 (LQT5) is a heart condition caused by defects in the KCNE1 gene, which encodes for a protein involved in potassium channel regulation. Potassium channels in the heart muscles are important for maintaining a consistent heartbeat Long QT refers to the elongation of the heartbeat, depicting an abnormal wave pattern on an electrocardiogram (ECG) seen with LQT patients. Such patients are at risk of episodes of increased heart rate, known as torsades de point, which may result in fainting or cardiac arrest. Death can sometimes occur, even in young people, so it is important that any fainting episodes are properly investigated. Treatments are by means of beta-blockers or implantable cardioverter-defibrillators (ICDs). Long QT syndrome types such as this, which only affect the heart, are also known as Romano-Ward syndrome.

Overall, it’s estimated that about 1 in 2,000 people, suffer from LQT, some without knowing it. The condition does not seem to be more prevalent in any ethnic group. LQT5 (KCNE1 gene) only makes up <1% of the total cases of LQT, leading to less than 1 in 200,000 having the condition. The affected gene is inherited in an autosomal dominant manner, which normally is inherited from one parent who also has the condition.

Sources

Alders, M. & Christiaans, I. (2003), “Long QT syndrome,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1129/

NIH, Genetics Home Reference: KCNE1 gene.

See http://ghr.nlm.nih.gov/gene/KCNE1

NIH, Genetics Home Reference: Romano-Ward Syndrome.

See http://ghr.nlm.nih.gov/condition/romano-ward-syndrome

Splawski, I. et al. (1997), “Mutations in the hminK gene cause long QT syndrome and suppress IKs function,” Nature Genetics, 17, 338-340.

See http://www.ncbi.nlm.nih.gov/pubmed/9354802

Tay-Sachs disease is caused by mutations in the HEXA gene, which encodes for one subunit of the enzyme beta-hexosaminidase A. The enzyme breaks down the toxic substance GM2 ganglioside in the brain and spinal cord. Symptoms usually develop from three months onwards, including loss of motor skills, increasing weakness, and strong startle response. Loss of vision and hearing, seizures, and paralysis normally follow. Life expectancy is 2 to 4 years. Very rare related diseases, which begin later in childhood, adolescence, or early adulthood are also known, but the symptoms are usually much milder. Tay-Sachs is rare in the general population, but tends to be concentrated in various ethnic groups. Among those of Ashkenazi Jewish descent, about 1 in 30 are carriers for the disease. There is also a high level of carriers in the Acadian (Cajun) population of Louisiana, and among French Canadians. However, extensive genetic counseling has led to a large reduction in the number of live births over recent decades. The faulty gene is autosomal recessive, typically requiring both parents to be asymptomatic carriers of the faulty gene copy.

Sources

Kaback, M.M. & Desnick, R.J. (1999), “Hexosaminidase A Deficiency,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1218/

NIH, Genetics Home Reference: HEXA gene.

See http://ghr.nlm.nih.gov/gene/HEXA

NIH, Genetics Home Reference: Tay-Sachs Disease.

See http://ghr.nlm.nih.gov/condition/tay-sachs-disease

Recombine Website. Tay-Sachs Disease.

See https://recombine.com/diseases/taysachs-disease

Maple syrup urine disease (MSUD) can be caused by mutations in a number of different genes, such as the BCKDHA gene. The BCKDHA gene encodes for the alpha subunit of the enzyme complex known as branched-chain alpha-keto acid dehydrogenase (BCKD), which is essential for the breakdown of branched chain amino-acids (leucine, isoleucine, and valine). Maple syrup urine disease is named due the sweet “maple syrup” smell from the urine of those with the disease. In the most common form of MSUD, untreated babies suffer from poor feeding and vomiting, followed by poor breathing, lethargy, and seizures. Death normally occurs within a few weeks of birth. Treatment is possible using special formula milk, followed by a special diet as an infant becomes older. However, it is difficult to always balance the amount of branched chain amino acids in the diet, since a small amounts must be supplied to maintain health. As they grow up, those with the condition tend to suffer from movement disorders, such as tremors, and various mental problems such as ADHD, low intelligence, autism, depression, and anxiety. In a minority of cases, the disease first shows itself later in infancy or during childhood, rather than immediately after birth. Some children suffer from an intermittent form of MSUD, where they appear normal most of the time, but attacks of the disease can be triggered by infections, stress, etc. Both the common form of the disease and the less severe forms can occur with defects in the BCKDA (Type 1A), BCKDB (Type 1B), and DBT (Type 2) genes; there is not a simple relation between severity and which gene is the cause. All types of Maple syrup urine disease occurs in about 1 in 185,000 live births worldwide. However, it is much more prevalent in old order Amish (BCKDHA defects) and Ashkenazi Jewish families (BCKDHB defects). The frequency of the disease reaches 1 in 380 live births in some old order Amish communities. The faulty gene is inherited in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers.

Sources

Edelmann, L. et al. (2001), “Maple syrup urine disease: identification and carrierfrequency determination of a novel founder mutation in the Ashkenazi Jewish population,” American Journal of Human Genetics, 69, 863-868.

See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1226071/

NIH, Genetics Home Reference: BCKDHA gene.

See http://ghr.nlm.nih.gov/gene/BCKDHA

NIH, Genetics Home Reference: Maple syrup urine disease.

See http://ghr.nlm.nih.gov/condition/maple-syrup-urine-disease

Strauss, K.A. et al. (2006), “Maple Syrup Urine Disease,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1319/

Recombine Website. Maple Syrup Urine Disease Type 1A.

See https://recombine.com/diseases/maple-syrup-urine-disease-type-1a

Usher syndrome is a condition that involves various degrees of deafness and gradual impairment of vision. Those with Usher syndrome type 1 are usually born deaf, and begin to lose vision while still children. A number of different genetic mutations can cause Usher syndrome type 1, including mutations in the MYO7A gene (Usher syndrome type 1B). MYO7A encodes for the protein myosin VIIA, which is involved in molecular transport. MYO7A is produced in the retina and inner ear, and is important for proper functioning. In the inner ear, it is involved in the production and maintenance of the hair-like stereocilia, which are essential for hearing. The vision loss from Usher’s syndrome is due to the condition retinitis pigmentosa, which involves the gradual deterioration of retinal rod photoreceptor cells (leading to night blindness), followed by cone receptor cells (leading eventually to complete blindness). In addition to deafness, Usher syndrome type 1 affects the ability to balance. Children with the condition are typically slow to stand up and walk. Usher syndrome type 1 affects overly 12,000 people in the USA alone. Roughly half of these are due to MYO7A mutations. Usher syndrome type 1 is more common in certain ethnic groups such as Ashkenazi Jews and the Acadians (Cajuns) of Louisiana. The condition is autosomal recessive, which typically requires both parents to be carriers, and usually are asymptomatic.

Sources

Keats, B.J.B. & Lentz, J. (1999), “Usher Syndrome Type 1,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1265/

NIH, Genetic Home Reference: MYO7A gene.

See http://ghr.nlm.nih.gov/gene/MYO7A

NIH, Genetics Home Reference: Usher syndrome.

See http://ghr.nlm.nih.gov/condition/usher-syndrome

Roux, A.-F. et al. (2006), “Survey of the frequency of USH1 gene mutations in a cohort of Usher patients shows the importance of cadherin 23 and protocadherin 15 genes and establishes a detection rate of above 90%,” Journal of Medical Genetics, 43, 763-768.

See http://jmg.bmj.com/content/43/9/763.abstract

Fanconi Anemia can be caused by defects in a number of genes, one of which is FANCA. This gene is involved in producing a protein involved in DNA repair, which it carries out via the so-called Fanconi anemia pathway. If the protein fails to function, DNA repair will not be carried out as normal, which can lead to many abnormalities, particularly affecting the bone marrow and blood cells. Patients have anemia and tend to suffer from infections. They are much more at risk of leukemia and other cancers than the general population. The majority of patients have one or more physical abnormalities, although a large minority are physically normal. A wide range of physical problems are possible. Common issues include short statue, unusual skin pigmentation, misshapen thumbs, microcephaly, eye defects, and deformed kidneys or genitals. The majority of those with the disease die before the age of 30. The overall incidence of Fanconi anemia is roughly 1 in 160,000, of which about 60- 70% are due to defects in the FANCA gene. Some populations, such as Spanish Roma, black South Africans, and Ashkenazi Jews, are at greater risk of the disease. Fanconi anemia type A is inherited in an autosomal recessive manner, typically requiring both parents to carry a faulty gene asymptomatically.

Sources

Alter, B.P. & Kupfer, G (2002), “Fanconi Anemia,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1401/

NIH, Genetics Home Reference: FANCA gene.

See http://ghr.nlm.nih.gov/gene/FANCA

NIH, Genetics Home Reference: Fanconi Anemia.

See http://ghr.nlm.nih.gov/condition/fanconi-anemia

Recombine Website: Fanconi Anemia Type A.

See https://recombine.com/diseases/fanconi-anemia-type-a

Non-syndromic hearing loss can be caused by mutations in a number of genes, including the COL11A2 gene (referred to as DFNA13 hearing loss). This gene encodes for part of Type XI collagen. Type XI collagen plays a vital role in the inner ear, thus mutations in COL11A2 can lead to poor hearing, as the collagen fibrils in the ear lack their normal structure. Patients with this non-progressive deficiency find it particularly difficult to hear mid-level frequencies, while retaining the ability to detect low and high frequencies. Initial studies focused on two families, one in the USA and one in the Netherlands. It is not yet possible to determine the prevalence of hearing loss due to COL11A2, although it seems to be rare. It is not clear whether any ethnic group is particularly affected. The condition is autosomal dominant which normally is inherited from at least one affected parent.

Sources

McGuirt, W.T. et al. (1999), “Mutations in COL11A2 cause non-syndromic hearing loss (DFNA13),” Nature Genetics, 23, 413-419.

See http://www.ncbi.nlm.nih.gov/pubmed/10581026

NIH, Genetic Home Reference: COL11A2 gene.

See http://ghr.nlm.nih.gov/gene/COL11A2

NIH, Genetics Home Reference: Nonsyndromic deafness.

See http://ghr.nlm.nih.gov/condition/nonsyndromic-deafness

Genetics is the study of heredity and the variations of inherited characteristics. More specifically, genetics is the study of how physical or mental characteristics are passed down from one generation to the next generation. DNA is the instruction manual found in every cell in our body. It is written in a language with only four letters, ATCG. Each person’s DNA is roughly 6 billion letters long. A gene is a small unit within the DNA that codes for a specific action in the body. As an analogy, if the DNA is an encyclopedia, then genes are specific entries inside the encyclopedia.

Long QT syndrome 6 (LQT6) is a heart condition caused by defects in the KCNE2 gene, which encodes for a protein involved in potassium channel regulation. Potassium channels in the heart muscles are important for maintaining a consistent heartbeat. Long QT refers to the elongation of the heartbeat, depicting an abnormal wave pattern on an electrocardiogram (ECG) seen with LQT patients. Such patients are at risk of episodes of increased heart rate, known as torsades de point, which can result in fainting or cardiac arrest. Death can sometimes occur, even in young people, so it’s important that any fainting episodes are properly investigated. Treatment is by means of beta-blockers or implantable cardioverter-defibrillators (ICDs). Long QT syndromes, which only affect the heart, are also known as Romano-Ward syndrome. Overall, it’s estimated that about 150,000 people suffer from LQT, some without knowing it. The condition does not seem to be more prevalent in any ethnic group. LQT6 (KCNE2 gene) only makes up <1% of the total cases of LQT, so less than 1 in 200,000, or 1,500 people, have the condition. The affected gene is inherited in an autosomal dominant manner, which normally is inherited from one parent who also has the condition.

Sources

Alders, M. & Christiaans, I. (2003), “Long QT syndrome,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1129/

NIH, Genetics Home Reference: KCNE2 gene.

See http://ghr.nlm.nih.gov/gene/KCNE2

NIH, Genetics Home Reference: Romano-Ward Syndrome.

See http://ghr.nlm.nih.gov/condition/romano-ward-syndrome

Hereditary cancer syndrome is when a person has a mutation in their genes that puts them at increased risk of developing cancer. This mutation can be passed down from parent to child.

Usher syndrome is a condition that involves various degrees of deafness and gradual impairment of vision. Those with Usher syndrome type 1 are usually born deaf, and begin to lose vision while still children. A number of different genetic mutations can cause Usher syndrome type 1, including mutations in the PCDH15 gene (Usher syndrome type 1F). PCDH15 encodes for the protein protocadherin 15, which is produced in the retina and inner ear, and is involved with cell adhesion. The vision loss from Usher’s syndrome is due to the condition retinitis pigmentosa, which involves the gradual deterioration of retinal rod receptor cells (leading to night blindness), followed by cone receptor cells (leading eventually to complete blindness). In addition to deafness, Usher syndrome type 1 affects the ability to balance. Children with the condition are typically slow to stand up and walk. The prevalence of Usher syndrome type 1 in the USA is over 4 in 100,000. Out of 34 families with Usher syndrome type 1, 6 were found to have defects in the PCDH15 gene. Usher syndrome type 1 is more common in certain ethnic groups, such as Ashkenazi Jews (where PCDH15 defects are believed to be particularly important) and the Acadians (Cajuns) of Louisiana. The condition is autosomal recessive, which typically requires an affected child to have two asymptomatic carrier parents.

Sources

Keats, B.J.B. & Lentz, J. (1999), “Usher Syndrome Type 1,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1265/

NIH, Genetic Home Reference: PCDH15 gene.

See http://ghr.nlm.nih.gov/gene/PCDH15

NIH, Genetics Home Reference: Usher syndrome.

See http://ghr.nlm.nih.gov/condition/usher-syndrome

Roux, A.-F. et al. (2006), “Survey of the frequency of USH1 gene mutations in a cohort of Usher patients shows the importance of cadherin 23 and protocadherin 15 genes and establishes a detection rate of above 90%,” Journal of Medical Genetics, 43, 763-768.

See http://jmg.bmj.com/content/43/9/763.abstract

Ehlers-Danlos Syndrome Type 4 is caused by mutations in the COL3A1 gene, which is one of a number of genes that control collagen production. The skin of those with the syndrome tends to bruise very easily. Blood vessels, the bowel, and the uterus have a high risk of perforations. Pregnancy is particularly risky for women with the syndrome. Sufferers tend to have highly visible blood vessels, particularly on the chest, and thin skin. The median age of death is about 48. The disease is autosomal dominant which typically requires at least one affected parent, and has a 50:50 chance of having the defect if one parent is affected. The occurrence of the syndrome is approximately 1 in 250,000 among the general population, and is equally prevalent among different ethnic groups.

Sources

The National Center for Biotechnology regarding Ehlers-Danlos Syndrome Type 4

See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1971255/

R. Jindel, A. Choong, D. Arul, S. Dhanjil, J. Chataway, N.J.W. Cheshire, “Vascular Manifestations of Type IV Ehlers–Danlos Syndrome” (2005).

See http://www.ejvesextra.com/article/S1533-3167(05)00047-6/fulltext

DNA sequencing is a tool used to discover the precise content and order of the genetic information encoded in DNA. The potential for medical use of DNA sequencing information is incredibly high, giving both doctors and patients key information to make more informed medical decisions.

Cystic Fibrosis is caused by defects in the CFTR gene, however defects in the SCNN1A gene can give similar symptoms. The SCNN1A gene encodes for a subunit of the epithelial sodium channel protein. In some cases a mutation on the CFTR gene may act together with a mutation on the SCNN1A gene to give a cystic fibrosislike disease. Patients have breathing difficulties due to sticky mucus that builds up in the lungs. They may also have severe digestive problems since digestive enzymes from the pancreas are blocked by thick mucus. Male sufferers may be infertile, due to the lack of functioning vas deferens tubes which transfer sperm to the urethra. Diabetes and liver disease are common complications that often develop over time. However, some of the symptoms may be absent with non-typical cystic fibrosis. Non-typical cystic fibrosis from SCNN1A mutations is a rare disease, but may be underreported. No reliable estimates are available for its prevalence.

Sources

John Hopkins Website: CF and CF-Related Disorders.

See http://www.hopkinsmedicine.org/dnadiagnostic/CF_CFRelated_Panel.htm

Mutesa, L., et al. (2009), “Genetic analysis of Rwandan patients with cystic fibrosislike symptoms: identification of novel cystic fibrosis transmembrane conductance regulator and epithelial sodium channel gene variants,” Chest, 135, 1233-1242.

See http://journal.publications.chestnet.org/article.aspx?articleid=1089797

NIH, Genetics Home Reference: Cystic Fibrosis.

See http://ghr.nlm.nih.gov/condition/cystic-fibrosis

NIH, Genetic Home Reference: SCNN1A gene. See http://ghr.nlm.nih.gov/gene/SCNN1A

Ramos, M.D. et al, (2014), “Extensive sequence analysis of CFTR, SCNN1A, SCNN1B, SCNN1G and SERPINA1 suggests an oligogenic basis for cystic fibrosislike phenotypes,” Clinical Genetics, 86, 91-95.

See http://onlinelibrary.wiley.com/doi/10.1111/cge.12234/references

Canavan disease is a disease affecting the brain, caused by defects in the ASPA gene. The gene encodes for the enzyme aspartoacylase, whose function is to decompose excess N-acetyl-L-aspartic acid (NAA) in the brain. If the enzyme fails to function, excess NAA interferes with the development of the myelin sheath, the insulating covering around axons which functions to increase speed of neural transmission. The most common form of Canavan Disease, the neonatal or infantile form, causes a failure to develop normal motor skills. They suffer from macrocephaly, hypotonia, and often irritability. Seizures and difficulty swallowing may occur. Children rarely survive beyond their teens, and many die earlier. A milder form of the disease, the juvenile form, sometimes occurs. This is associated with slower than normal development of speech and motor skills, but does not normally lead to severe symptoms or a shortened lifespan. Canavan disease is most common in those of Ashkenazi Jewish descent, where it is estimated to occur in 1 in 6,400 to 1 in 13,500 births. The incidence in the general population is much lower, but accurate estimates are not available. The disease is inherited as autosomal recessive, which typically requires both parents to be carriers of the faulty gene, most likely asymptomatically.

Sources

Matalon, R. & Michals-Matalon, K. (1999), “Canavan Disease,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1234/

NIH, Genetics Home Reference: ASPA gene.

See http://ghr.nlm.nih.gov/gene/ASPA

NIH, Genetics Home Reference: Canavan disease.

See http://ghr.nlm.nih.gov/condition/canavan-disease

Maple syrup urine disease (MSUD) can be caused by mutations in a number of different genes, such as the BCKDHB gene. The BCKDHB gene encodes for the beta subunit of the enzyme complex known as branched-chain alpha-keto acid dehydrogenase (BCKD), which is essential for the breakdown of branched chain amino-acids (leucine, isoleucine, and valine). Maple syrup urine disease is named due the sweet “maple syrup” smell from the urine of those with the disease. In the most common form of MSUD, untreated babies suffer from poor feeding and vomiting, followed by poor breathing, lethargy, and seizures. Death normally occurs within a few weeks of birth. Treatment is possible using special formula milk, followed by a special diet as an infant becomes older. However, it is difficult to always balance the amount of branched chain amino acids in the diet, since a small amounts must be supplied to maintain health. As they grow up, those with the condition tend to suffer from movement disorders, such as tremors, and various mental problems, such as ADHD, low intelligence, autism, depression, and anxiety. In a minority of cases, the disease first shows itself later in infancy or during childhood, rather than immediately after birth. Some children suffer from an intermittent form of MSUD, where they appear normal most of the time, but attacks of the disease can be triggered by infections, stress, etc. Both the common form of the disease and the less severe forms can occur with defects in the BCKDA (Type 1A), BCKDB (Type 1B), and DBT (Type 2) genes; there is not a simple relation between severity and which gene is the cause. Maple syrup urine disease (all types) occurs in about 1 in 185,000 live births worldwide. However, it is much more prevalent in old order Amish (BCKDHA defects) and those of Ashkenazi Jewish descent (BCKDHB defects). The faulty gene is inherited in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers.

Sources

Edelmann, L. et al. (2001), “Maple syrup urine disease: identification and carrierfrequency determination of a novel founder mutation in the Ashkenazi Jewish population,” American Journal of Human Genetics, 69, 863-868.

See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1226071/

NIH, Genetics Home Reference: BCKDHB gene.

See http://ghr.nlm.nih.gov/gene/BCKDHB

NIH, Genetics Home Reference: Maple syrup urine disease.

See http://ghr.nlm.nih.gov/condition/maple-syrup-urine-disease

Recombine Website. Maple Syrup Urine Disease Type 1B.

See https://recombine.com/diseases/maple-syrup-urine-disease-type-1b

Strauss, K.A. et al. (2006), “Maple Syrup Urine Disease,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1319/

Non-syndromic hearing loss can be caused by mutations in a number of genes, including the GJB2 gene, which causes what is known as DFNB1 deafness. The GJB2 gene encodes for a protein called connexin 26 (also known as gap junction beta 2), which is involved in producing gap junctions for the transport of ions, nutrients, and other important functions. Faulty connexin 26 in the inner ear can lead to hearing loss or deafness. The degree of hearing loss can vary widely between affected individuals. The disease is not progressive. The faulty GBJ2 gene is autosomal recessive, which typically requires both parents to be carriers of the faulty gene, usually occurring asymptomatically. DFNB1 deafness (i.e. deafness from the GJB2 gene, in around 98% of cases) is estimated to affect around 42,000 people in the USA/ Western Europe. Some ethnic groups, such as Palestinians, Iran Kurds, and Siberian Altaians have particularly high levels of the faulty gene.

Sources

NIH, Genetic Home Reference: GJB2 gene.

See http://ghr.nlm.nih.gov/gene/GJB2

NIH, Genetics Home Reference: Nonsyndromic deafness.

See http://ghr.nlm.nih.gov/condition/nonsyndromic-deafness

Smith, R.J.H. & Van Camp, G. (1998), “Nonsyndromic hearing loss and deafness: DFNB1,” in Pagon, R.A. et al., editors, GeneReview [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1272/

Spinal muscular atrophy (SMA) can be caused by mutations in a number of genes. One of these is the SMN1 gene, which encodes for the spinal motor neuron protein. This protein is required for the maintenance of motor neurons in the spinal cord and brainstem. The SMN2 gene is also capable, to some extent, of producing spinal neuron protein. Most people have two or fewer copies of the SMN2 gene. However, some have three or more copies. In this latter group, the extra copies of the SMN2 gene can moderate the effects of mutations in the SMN1 gene, making any resulting SMA disease less severe than it would otherwise have been. SMA is divided into different types: types 1-4 of SMA are all caused by mutations of the SMN1 gene, and all involve muscle weakness. Type 1 SMA first occurs before 6 months. Affected babies are unable to hold their heads up or sit up. They typically have difficulty swallowing and breathing, and tend not to survive beyond the age of two. Type 2 SMA first occurs between 6 months and a year. Babies can sit up, but do not go on to stand or walk unaided in the usual manner. Type 3 SMA first occurs in older children. They can normally walk unaided, but may find climbing stairs or other similar tasks difficult. They may need to use a wheelchair by mid-life. It has been shown that patients from type 3 SMA are much more likely to have 3 or more copies of the SMN2 gene than patients from type 1 or the general population. Type 4 SMA first occurs in adulthood. Sufferers have some muscle weakness, tremors, and mild breathing problems. The incidence of all types of spinal muscular atrophy is around 1 in 6,000 to 1 in 10,000 births. It is estimated that around 1 in 40 to 1 in 50 people is a carrier. Although the incidence varies somewhat from country to country, it does not seem to be highly present in any ethnic group. The faulty SMN1 gene is transmitted in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers.

Sources

Mailman, M.D. et al. (2002), “”Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2,” Genetics in Medicine, 4, 20-26.

See http://www.nature.com/gim/journal/v4/n1/full/gim20024a.html

NIH, Genetics Home Reference: SMN1 gene.

See http://ghr.nlm.nih.gov/gene/SMN1

NIH, Genetics Home Reference: SMN1 gene.

See http://ghr.nlm.nih.gov/gene/SMN2

NIH, Genetics Home Reference: Spinal Muscular Atrophy.

See http://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy

Prior, T.W. & Russman, B.S., (2000), “Spinal Muscular Atrophy,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1352/

Recombine Website. Spinal Muscular Atrophy: SMN1 linked.

See https://recombine.com/diseases/spinal-muscular-atrophy-smn1-linked

Niemann-Pick Disease Type C2 is caused by mutations in the NPC2 gene. This gene is involved in producing a protein involved in the transportation of lipids, including cholesterol. Mutations in the NPC1 gene cause similar effects (Type C1, which is much more common). Symptoms of Niemann Pick C2 typically develop in early childhood, but can first appear in adults. Muscle weakness and ataxia (poor control of movements, etc.) become gradually apparent, along with liver disease, seizures (in some cases), and progressive mental deterioration. Sufferers are often unable to move their eyes vertically (vertical supranuclear gaze palsy). Swallowing and speech deteriorate progressively, leading to a complete inability to ingest food. Respiratory failure can also occur. Early death is likely, although some sufferers live for many decades. When the disease first appears in adulthood, psychiatric symptoms tend to predominate. The total incidence of Niemann-Pick disease Type C is around 1 in 120,000 births, translating to 2,500 occurrences in the USA. About 4-5% are due to the NPC2 gene. The defective genes are inherited in an autosomal recessive manner, typically requiring both parents to carry the faulty gene asymptomatically.

Sources

NIH, Genetics Home Reference: NCP2 gene.

See http://ghr.nlm.nih.gov/gene/NPC2

NIH, Genetics Home Reference: Niemann-Pick Disease.

See http://ghr.nlm.nih.gov/condition/niemann-pick-disease

Patterson, M. (2000), “Neimann-Pick Disease Type C,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1296/

Recombine Website: Niemann-Pick Disease Type C2.

See https://recombine.com/diseases/niemann-pick-disease-type-c2

Fanconi Anemia can be caused by defects in a number of genes, one of which is FANCC. This gene is involved in producing a protein involved in DNA repair, which it carries out via the so-called Fanconi anemia pathway. If the protein fails to function, DNA repair will not be carried out as normal, which can lead to many abnormalities, particularly affecting the bone marrow and blood cells. Sufferers have anemia and tend to suffer from infections. They are much more at risk of leukemia and other cancers than the general population. The majority of sufferers have one or more physical abnormalities, although a large minority are physically normal. A wide range of physical problems are possible. Common issues include short statue, unusual skin pigmentation, misshapen thumbs, microcephaly, eye defects, and deformed kidneys or genitals. The majority of those with the disease die before the age of 30. The overall incidence of Fanconi anemia is roughly 1 in 160,000, of which about 14% are due to defects in the FANCC gene. Some populations, such as Spanish Roma, black South Africans, and Ashkenazi Jews, are at greater risk of the disease. There is high incidence of Fanconi anemia type C in the latter community, the carrier rate being about 1 in 100. Fanconi anemia type C is inherited in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers.

Sources

Alter, B.P. & Kupfer, G (2002), “Fanconi Anemia,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1401/

NIH, Genetics Home Reference: FANCC gene.

See http://ghr.nlm.nih.gov/gene/FANCC

NIH, Genetics Home Reference: Fanconi Anemia.

See http://ghr.nlm.nih.gov/condition/fanconi-anemia

Recombine Website: Fanconi Anemia Type C.

See https://recombine.com/diseases/fanconi-anemia-type-c

Familial TAAD can be caused by mutations in the ACTA2 gene. This gene accounts for around 10-20% of cases of familial TAAD. The gene encodes for the protein α-2 actin, which is a component of smooth muscle cells in arterial walls. Along with the ACTA2 gene, other known and unknown genes can also cause familial TAAD. In patients with TAAD, the aorta increases in diameter, which may cause dissection, or blood flowing through the artery wall following a tear. Rupture of the artery may follow, often leading to rapid death. Surgery is often required where a significant thoracic aortic aneurysm occurs. Families with ACTA2 abnormalities are also more prone to occlusive vascular disease and livedo reticularis, a skin disease. With proper management, life expectancy for those with familial TAAD can approach that of the general population. The ACTA2 gene defects that cause familial TAAD are autosomal dominant. Typically, an affected person has one affected parent. However, it is possible for the defective gene to be carried without any TAAD occurring in a situation known as reduced penetrance. Overall, familial TAAD is estimated to cause roughly 20% of thoracic aortic aneurysms and dissections. Approximately 10,000 deaths per year occur due to TAAD in the USA; about 2,000 will be due to familial TAAD, giving around 200-400 deaths per year from ACTA2 defects, out of an overall USA total of around 2.6 million (0.01 to 0.02% of total deaths).

Sources

NIH, Genetics Home Reference: Familial thoracic aortic aneurysm and dissection.

See https://ghr.nlm.nih.gov/condition/familial-thoracic-aortic-aneurysm-and-dissection

Next-Generation sequencing (NGS), or Next-Gen sequencing, is a specific sequencing technique that has taken the research world by storm since its inception in the early 2000’s. With its ability to sequence quickly and efficiently, NGS is the perfect technique to provide medical professionals with important genetic information about their patients in a timely manner.

Maple syrup urine disease (MSUD) can be caused by mutations in a number of different genes, such as the DBT gene. The DBT gene encodes for the E2 component of the enzyme complex known as branched-chain alpha-keto acid dehydrogenase (BCKD), which is essential for the breakdown of branched chain amino-acids (leucine, isoleucine, and valine). Maple syrup urine disease is named due the sweet “maple syrup” smell from the urine of those with the disease. In the most common form of MSUD, untreated babies suffer from poor feeding and vomiting, followed by poor breathing, lethargy, and seizures. Death normally occurs within a few weeks of birth. Treatment is possible using special formula milk, followed by a special diet as an infant becomes older. However, it is difficult to always balance the amount of branched chain amino acids in the diet, since a small amounts must be supplied to maintain health. As they grow up, those with the condition tend to suffer from movement disorders, such as tremors, and various mental problems such as ADHD, low intelligence, autism, depression, and anxiety. In a minority of cases, the disease first shows itself later in infancy or during childhood, rather than immediately after birth. Some children suffer from an intermittent form of MSUD, where they appear normal most of the time, but attacks of the disease can be triggered by infections, stress, etc. Both the most common form of the disease and the less severe forms can occur with defects in the BCKDA (Type 1A), BCKDB (Type 1B), and DBT (Type 2) genes; there is not a simple relation between severity and which gene is the cause. All types of Maple syrup urine disease occur in about 1 in 185,000 live births worldwide. However, it is much more prevalent in old order Amish (BCKDHA defects) and those of Ashkenazi Jewish descent (BCKDHB defects). The faulty gene is inherited in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers.

Sources

Edelmann, L. et al. (2001), “Maple syrup urine disease: identification and carrierfrequency determination of a novel founder mutation in the Ashkenazi Jewish population,” American Journal of Human Genetics, 69, 863-868.

See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1226071/

NIH, Genetics Home Reference: DBT gene.

See http://ghr.nlm.nih.gov/gene/DBT

NIH, Genetics Home Reference: Maple syrup urine disease.

See http://ghr.nlm.nih.gov/condition/maple-syrup-urine-disease

Strauss, K.A. et al. (2006), “Maple Syrup Urine Disease,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1319/

Spinal muscular atrophy (SMA) can be caused by mutations in a number of genes, most commonly the SMN1 gene. However, it can also be caused by the UBA1 gene, which encodes for the ubiquitin-activating enzyme E1. SMA from UBA1 is referred to as X-linked SMA, as the gene resides on the X chromosome. This ubiquitin-activating enzyme breaks down unwanted proteins which can damage motor neurons responsible for muscle movement. Babies usually exhibit muscle weakness from birth, and are prone to lung disease and bone fractures. Typically, breathing becomes progressively more difficult, and very few survive childhood. Other types of SMA are the result of SMN1 mutations. Type 1 SMA first occurs before 6 months. Affected babies are unable to hold their heads up or sit up. They typically have difficulty swallowing and breathing, so tend not to survive beyond the age of two. Type 2 SMA first occurs between 6 months and a year. Babies can sit up, but do not go on to stand or walk unaided in the usual manner. Type 3 SMA first occurs in older children. They can normally walk unaided, but may find climbing stairs or other similar tasks difficult. They may need to use a wheelchair by mid-life. Type 4 SMA first occurs in adulthood. Sufferers have some muscle weakness, tremors, and mild breathing problems. The incidence of spinal muscular atrophy (all types) is around 1 in 6,000 to 1 in 10,000 births. However, SMA caused by the UBA1 gene is very rare. Less than 20 families with this condition have been found by researchers. The gene is on the Xchromosome, which affects males far more than females, as males only have one Xchromosome, and are affected by the disease if the chromosome carries a mutated UBA1 gene. For females, both X-chromosomes need to have a mutated UBA1 gene for the disease to occur, which is very unlikely. A woman with a mutated UBA1 gene on one X-chromosome can act as a carrier without showing symptoms.

Sources

Baumbach-Reardon, L. et al. (2008), “Spinal Muscular Atrophy, X-Labelled Infantile,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK2594/

NIH, Genetics Home Reference: Spinal Muscular Atrophy.

See http://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy

NIH, Genetics Home Reference: UBA1 gene.

See http://ghr.nlm.nih.gov/gene/UBA1

Non-syndromic hearing loss can be caused by mutations in a number of genes, including the GJB3 gene, which causes what is known as DFNA2B deafness. The GJB3 gene encodes for a protein called connexin 31 (also known as gap junction beta 3), which is involved in producing gap junctions for the transport of ions, nutrients, etc. Faulty connexin 31 in the inner ear can lead to hearing loss or deafness. Hearing loss is particularly marked in the higher frequencies. No reliable data on prevalence are available. The genetic defect and associated hearing loss were found in two Chinese families. There have been no subsequent reports on any such association, suggesting that it may be very rare. The faulty gene is autosomal dominant, which typically requires at least one affected parent.

Sources

NIH, Genetic Home Reference: GJB3 gene.

See http://ghr.nlm.nih.gov/gene/GJB3

NIH, Genetics Home Reference: Nonsyndromic deafness.

See http://ghr.nlm.nih.gov/condition/nonsyndromic-deafness

Smith, R.J.H. & Hilderbrand, M. (2008), “DFNA2 nonsyndromic hearing loss,” in Pagon, R.A. et al., editors, GeneReview [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1209/

Xia, J.H. et al. (1998), “Mutations in the gene encoding gap junction protein beta-3 associated with autosomal dominant hearing impairment.” Nature Genetics, 20, 370- 373.

See https://www.ncbi.nlm.nih.gov/pubmed/9843210

Sickle cell disease is caused by mutations in the HBB gene, which encodes for the protein beta-globin, a component of hemoglobin. The main form of the disease is sickle cell anemia, where the red blood cells are bent into a sickle shape. Sickle cells break down more quickly than normal cells, often resulting in anemia. The irregular cell shape tends to block blood vessels, which can lead to pain and ischemia of organs, including strokes. Jaundice and damage to the spleen often occur. In some cases, pulmonary hypertension can occur and lead to heart failure. Other than sickle cell formation, other abnormal forms of hemoglobin can form. The various symptoms of sickle cell anemia shorten live expectancy to about 40 to 60 years. Sickle cell disease tends to be concentrated in particular ethnic groups. About 1 in 500 African Americans have sickle cell disease, while the figure is about 1 in 1,000 to 1 in 1,400 for Hispanic Americans. In all about 100,000 Americans suffer from sickle cell disease. As the population of the USA is around 321 million, this means that about 1 in 3210 Americans has the disease, making it the most common inherited blood disease. The faulty gene is autosomal recessive, typically requiring both parents to be asymptomatic carriers of the faulty gene copy.

Sources

Bender M.A. & Seibel, G.D. (2003), “Sickle Cell Disease,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1377/

NIH, Genetics Home Reference: HBB gene.

See http://ghr.nlm.nih.gov/gene/HBB

NIH, Genetics Home Reference: Sickle Cell Disease.

See http://ghr.nlm.nih.gov/condition/sickle-cell-disease

Recombine Website. Sickle Cell Anemia.

See https://recombine.com/diseases/sickle-cell-anemia

US Census Bureau http://www.census.gov/popclock/

Long QT syndrome 1 (LQT1) is a heart condition caused by defects in the KCNQ1 gene, which encodes for a protein involved with potassium channels, which are fundamental for maintaining a consistent heartbeat. Long QT refers to the elongation of the heartbeat, depicting an abnormal wave pattern on an electrocardiogram (ECG) seen with LQT patients. Such patients are at risk of episodes of increased heart rate, known as torsades de point, which can result in fainting or cardiac arrest. Death can sometimes occur, even in young people, so it’s important that any fainting episodes are properly investigated. Treatment is by means of beta-blockers or implantable cardioverter-defibrillators (ICDs). Long QT syndrome types such as this, which only affect the heart, are also known as Romano-Ward syndrome. Overall, it’s estimated that about 1 in 2,000 people suffer from LQT, translating to approximately 150,000 cases. The condition does not seem to be more prevalent in any ethnic group. LQT1 makes up 30 to 35% of the total cases of LQT, so roughly 1 in 6,000, or 50,000 cases, have the condition caused by the KCNQ1 gene. The affected gene is inherited in an autosomal dominant manner, which normally is inherited from one parent who also has the condition.

Sources

Alders, M. & Christiaans, I. (2003), “Long QT syndrome,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1129/

NIH, Genetics Home Reference: KCNQ1 gene.

See http://ghr.nlm.nih.gov/gene/KCNQ1

NIH, Genetics Home Reference: Romano-Ward Syndrome.

See http://ghr.nlm.nih.gov/condition/romano-ward-syndrome

Usher syndrome is a condition that involves various degrees of deafness and gradual impairment of vision. Those with Usher syndrome type 1 are usually born deaf, and begin to lose vision while still children. A number of different genetic mutations can cause Usher syndrome type 1, including mutations in the USH1C gene (Usher syndrome type 1C). USH1C encodes for the scaffold protein harmonin, which is produced in the retina and inner ear. It has a vital role in the stereocilia, the hair-like structures in the inner ear which are essential for stimulating neural pathways responsible for hearing. The vision loss from Usher’s syndrome is due to the condition retinitis pigmentosa, which involves the gradual deterioration of retinal rod photoreceptor cells (leading to night blindness), followed by cone receptor cells (leading eventually to complete blindness). In addition to deafness, Usher syndrome type 1 affects the ability to balance. Children with the condition are typically slow to stand up and walk. The prevalence of Usher syndrome type 1 in the USA is over 4 in 100,000. Out of 34 families with Usher syndrome type 1, only 2 were found to have defects in the USH1C gene. Usher syndrome type 1 is more common in certain ethnic groups, such as Ashkenazi Jews and the Acadians (Cajuns) of Louisiana. In the latter group, mutations of the USH1C gene are the main cause of the disease, although the gene is a minor cause for other populations. The condition is autosomal recessive, so typically an affected child will have two asymptomatic carrier parents.

Sources

Keats, B.J.B. & Lentz, J. (1999), “Usher Syndrome Type 1,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1265/

NIH, Genetic Home Reference: USH1C gene.

See http://ghr.nlm.nih.gov/gene/USH1C

NIH, Genetics Home Reference: Usher syndrome.

See http://ghr.nlm.nih.gov/condition/usher-syndrome

Roux, A.-F. et al. (2006), “Survey of the frequency of USH1 gene mutations in a cohort of Usher patients shows the importance of cadherin 23 and protocadherin 15 genes and establishes a detection rate of above 90%,” Journal of Medical Genetics, 43, 763-768.

See http://jmg.bmj.com/content/43/9/763.abstract

Cystic Fibrosis is caused by defects in the CFTR gene, however defects in the SCNN1B gene can give similar symptoms. The SCNN1B gene encodes for a subunit of the epithelial sodium-channel protein. In some cases a mutation on the CFTR gene may act together with a mutation on the SCNN1B gene to give a cystic fibrosislike disease. Sufferers have breathing difficulties, due to sticky mucus buildup in the lungs. They may also have severe digestive problems, since digestive enzymes from the pancreas are blocked from entering the small intestine, the main location of nutrient absorption. Male sufferers may be infertile, due to the lack of functioning vas deferens tubes which lead to the urethra. Diabetes and liver disease are common complications that often develop over time. However, some of the symptoms may be absent with non-typical cystic fibrosis. Non-typical cystic fibrosis from SCNN1B mutations is a rare disease, but may be underreported. No reliable estimates are available for its prevalence.

Sources

John Hopkins Website: CF and CF-Related Disorders.

See http://www.hopkinsmedicine.org/dnadiagnostic/CF_CFRelated_Panel.htm

Mutesa, L., et al. (2009), “Genetic analysis of Rwandan patients with cystic fibrosislike symptoms: identification of novel cystic fibrosis transmembrane conductance regulator and epithelial sodium channel gene variants,” Chest, 135, 1233-1242.

See http://journal.publications.chestnet.org/article.aspx?articleid=1089797

NIH, Genetics Home Reference: Cystic Fibrosis.

See http://ghr.nlm.nih.gov/condition/cystic-fibrosis

NIH, Genetic Home Reference: SCNN1B gene.

See http://ghr.nlm.nih.gov/gene/SCNN1B

Ramos, M.D. et al, (2014), “Extensive sequence analysis of CFTR, SCNN1A, SCNN1B, SCNN1G and SERPINA1 suggests an oligogenic basis for cystic fibrosislike phenotypes,” Clinical Genetics, 86, 91-95.

See http://onlinelibrary.wiley.com/doi/10.1111/cge.12234/references

Fanconi Anemia can be caused by defects in a number of genes, one of which is FANCF. This gene is involved in producing a protein involved in DNA repair, which it carries out via the so-called Fanconi anemia pathway. If the protein fails to function, DNA repair will not be carried out as normal, which can lead to many abnormalities, particularly affecting the bone marrow and blood cells. Patients have anemia and tend to suffer from infections. They are much more at risk of leukemia and other cancers than the general population. The majority of sufferers have one or more physical abnormalities, although a large minority are physically normal. A wide range of physical problems are possible. Common issues include short statue, unusual skin pigmentation, misshapen thumbs, microcephaly, eye defects, and deformed kidneys or genitals. The majority of those with the disease die before the age of 30. The overall incidence of Fanconi anemia is roughly 1 in 160,000, of which about 2% are due to defects in the FANCF gene. Some populations, such as Spanish Roma, black South Africans, and Ashkenazi Jews, are at greater risk of the disease. Fanconi anemia type F is inherited in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers.

Sources

Alter, B.P. & Kupfer, G (2002), “Fanconi Anemia,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1401/

NIH, Genetics Home Reference: FANCF gene.

See http://ghr.nlm.nih.gov/gene/FANCF

NIH, Genetics Home Reference: Fanconi Anemia.

See http://ghr.nlm.nih.gov/condition/fanconi-anemia

No. A positive result on the cancer screen is not a diagnosis of cancer.

Spinal muscular atrophy (SMA) can be caused by mutations in a number of genes, usually the SMN1 gene. However, a few cases of adult-onset SMA have been linked to mutations in the VAPB gene, which produces the protein named “VAMP-associated protein B and C.” Those with SMA from VAPB mutations begin to suffer from progressive muscle weakness, and may have cramps, tremors, and swallowing or breathing difficulties. Symptoms can begin at any age between 20 and 60. SMA from SMN1 defects is divided into different types, types 1-4: all involve muscle weakness. Type 1 SMA first occurs before 6 months. Affected babies are unable to hold their heads up or sit up. They typically have difficulty swallowing and breathing, so tend not to survive beyond the age of two. Type 2 SMA first occurs between 6 months and a year. Babies can sit up, but do not go on to stand or walk unaided in the usual manner. Type 3 SMA first occurs in older children. They can normally walk unaided, but may find climbing stairs or other similar tasks difficult. They may need to use a wheelchair by mid-life. Type 4 SMA first occurs in adulthood. Sufferers have some muscle weakness, tremors, and mild breathing problems. The incidence of spinal muscular atrophy (all types) is around 1 in 6,000 to 1 in 10,000 births. However, the adult-onset form related to the VAPB gene is much rarer, having only been found in a small number of families. The faulty gene is transmitted in an autosomal dominant manner, typically requiring at least one affected parent. If an asymptomatic parent died at a relatively young age, it is possible that the disease did not have time to present itself. The faulty gene is also associated with some cases of ALS (amyotrophic lateral sclerosis), also known as Lou Gehrig’s disease.

Sources

NIH, Genetics Home Reference: Spinal Muscular Atrophy.

See http://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy

NIH, Genetics Home Reference: VAPB gene.

See http://ghr.nlm.nih.gov/gene/VAPB

Nishimura, A.L. et al. (2004), “A Mutation in the Vesicle-Trafficking Protein VAPB Causes Late-Onset Spinal Muscular Atrophy and Amyotrophic Lateral Sclerosis,” American Journal of Human Genetics, 75, 822-831.

See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182111/

Richieri-Costa, A. et al. (1981), “Autosomal dominant late adult spinal muscular atrophy, type Finkel,” American Journal of Medical Genetics, 9, 119-128.

See http://www.ncbi.nlm.nih.gov/pubmed/7258225

Congenital aneurysms (widening of blood vessels) can be caused by mutations in the COL4A1 gene. This gene codes for the alpha-1 (IV) chain of type IV collagen. Defects in the gene can lead to cerebral aneurysms and strokes, due to a condition known as COL4A1-related brain small vessel disease. Damage to blood vessels can lead to various eye disorders. Defects in the gene can also cause porencephaly (fluid filled areas in the brain). A syndrome known as HANAC, hereditary angiopathy with nephropathy, aneurysms and muscle cramps, may also occur. Here, the kidneys are damaged, eye problems are common, aneurysms may occur in the brain and elsewhere, and the patient suffers frequent muscle cramps. The various conditions caused by COL4A1 defects all give increased risk of premature death, typically from strokes. The defective gene is autosomal dominant. Affected people typically have one affected parent. Diseases caused by defects in the COL4A1 gene are very rare. Less than 100 individuals with such diseases have been identified, all from Europe or North America.

Sources

Natural Institute of Neurological Disorders and Stroke

See http://www.ninds.nih.gov/disorders/cerebral_aneurysm/detail_cerebral_aneurysms.htm

National Center for Biotechnology regarding mutations of the COLA1 gene

See http://www.ncbi.nlm.nih.gov/books/NBK7046/

Fanconi Anemia can be caused by defects in a number of genes, one of which is FANCG. This gene is involved in producing a protein involved in DNA repair, which it carries out via the so-called Fanconi anemia pathway. If the protein fails to function, DNA repair will not be carried out as normal, which can lead to many abnormalities, particularly affecting the bone marrow and blood cells. Sufferers have anemia and tend to suffer from infections. They are much more at risk of leukemia and other cancers than the general population. The majority of patients have one or more physical abnormalities, although a large minority are physically normal. A wide range of physical problems are possible. Common ones include short statue, unusual skin pigmentation, misshapen thumbs, microcephaly, eye defects, and deformed kidneys or genitals. The majority of those with the disease die before the age of 30. The various types of the disease produce similar symptoms, although there is some evidence that leukemia is more likely to develop with Type G. The overall incidence of Fanconi anemia is roughly 1 in 160,000, of which about 10% are due to defects in the FANCG gene. Some populations, such as Spanish Roma, black South Africans, and Ashkenazi Jews, are at greater risk of the disease. Fanconi anemia type G is inherited in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers.

Sources

Alter, B.P. & Kupfer, G (2002), “Fanconi Anemia,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1401/

NIH, Genetics Home Reference: FANCG gene.

See http://ghr.nlm.nih.gov/gene/FANCG

NIH, Genetics Home Reference: Fanconi Anemia.

See http://ghr.nlm.nih.gov/condition/fanconi-anemia

Recombine Website: Fanconi Anemia Type G.

See https://recombine.com/diseases/fanconi-anemia-type-g

Long QT syndrome 3 (LQT3), is a heart condition caused by defects in the SCN5A gene, which encodes for a protein, sodium channel voltage gated type V alpha subunit, that makes up sodium channels. Such channels in the heart muscles are important for maintaining a regular heartbeat. Long QT refers to the elongation of the heartbeat, depicting an abnormal wave pattern on an electrocardiogram (ECG) seen with LQT patients. Such patients are at risk of episodes of increased heart rate, known as torsades de point, which can result in fainting or cardiac arrest. Death can sometimes occur, even in young people, so it’s important that any fainting episodes are properly investigated. Treatment is by means of beta-blockers or implantable cardioverter-defibrillators (ICDs). Long QT syndrome types such as this, which only affect the heart, are also known as Romano-Ward syndrome. Overall, it’s estimated that about 1 in 2,000, or 150,000 people, suffer from LQT, some without knowing it. The condition does not seem to be more prevalent in any ethnic group. LQT3 makes up 5 to 10% of the total cases of LQT, roughly 1 in 20,000 to 1 in 40,000 have the condition caused by the SCN5A gene. The affected gene is inherited in an autosomal dominant manner, which normally is inherited from one parent who also has the condition.

Sources

Alders, M. & Christiaans, I. (2003), “Long QT syndrome,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1129/

NIH, Genetics Home Reference: SCN5A gene.

See http://ghr.nlm.nih.gov/gene/SCN5A

NIH, Genetics Home Reference: Romano-Ward Syndrome.

See http://ghr.nlm.nih.gov/condition/romano-ward-syndrome

Usher syndrome is a condition that involves various degrees of deafness and gradual impairment of vision. Those with Usher syndrome type 2 are usually born with some hearing impairment: typically they cannot hear higher frequencies. Progressive vision loss occurs slowly from the teenage years onwards, although some vision may be retained for many decades. A number of different genetic mutations can cause Usher syndrome type 2, including those of the USH2A gene (Usher syndrome type 2A). USH2A encodes for the protein usherin, which forms basement membranes in the inner ear and retina. The vision loss from Usher’s syndrome is due to the condition retinitis pigmentosa, which involves the gradual deterioration of retinal rod photoreceptor cells (leading to night blindness), followed by cone receptor cells (affecting day time vision as well). Unlike Usher syndrome type 1, Usher syndrome type 2 does not affect a child’s balance or their ability to stand up and walk. The prevalence of Usher syndrome type 2 in the USA is unknown, but it is believed to be more common than type 1, which occurs in over 4 in 100,000 people. The large number of relatively mild cases of type 2 mean that it is difficult to obtain accurate figures. It is estimated that 57-79% of Usher syndrome type 2 cases are caused by mutations in the USH2A gene. The condition is autosomal recessive, so typically an affected child will have two asymptomatic carrier parents.

Sources

Keats, B.J.B. & Lentz, J. (1999), “Usher Syndrome Type II,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1341/

NIH, Genetic Home Reference: USH2A gene.

See http://ghr.nlm.nih.gov/gene/USH2A

NIH, Genetics Home Reference: Usher syndrome.

See http://ghr.nlm.nih.gov/condition/usher-syndrome

Gaucher Disease is caused by mutations in the GBA gene. This gene encodes for the enzyme beta-glucocerebrosidase, which breaks down the substance glucocerebroside. The buildup of glucocerebroside causes damage to various organs. There are various types of Gaucher disease. Type 1 is the most common, and involves anemia, lung disease, enlargement of the spleen and liver, easy bruising of the skin, and skeletal disorders such as arthritis and high risk of fractures. The nervous system is not affected in type 1 Gaucher disease. Types 2 and 3 involve serious damage to the nervous system, with type 2 being the more aggressive, leading normally to early mortality. A perinatal form of the disease is also known, leading to prompt death after birth. Finally, a cardiovascular form of the disease mainly involves damage to the heart valves. In the general population, Gaucher disease is found in 1 in 60,000 to 1 in 80,000 new births. It is much more prevalent in various ethnic groups. Among those of Ashkenazi Jewish descent, the disease is found in 1 in 855 people (nearly all Type 1), with around 1 in 18 people being carriers. The disease is autosomal recessive, typically requiring both parents to be asymptomatic carriers of the faulty gene copy.

Sources

Pastores, G.M. & Hughes, D.A. (2000), “Gaucher Disease,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1269/

NIH, Genetic Home Reference: GBA gene.

See http://ghr.nlm.nih.gov/gene/GBA

NIH, Genetics Home Reference: Gaucher.

See http://ghr.nlm.nih.gov/condition/gaucher-disease

Recombine Website. Gaucher Disease.

See https://recombine.com/diseases/gaucher-disease

Non-syndromic hearing loss can be caused by mutations in a number of genes, including the KCNQ4 gene, which causes what is known as DFNA2 deafness. The KCNQ4 gene encodes for a protein called potassium voltage-gated channel KQTlike protein 4, which is involved in potassium ion channel formation, particularly in the inner ear and auditory nerve. Hearing is particularly poor for high frequencies, but better for lower frequencies. The condition is progressive, and most patients will have to start wearing a hearing aid between the ages of 10 and 40. No reliable data on prevalence are available. There is no evidence that mutations in KCNQ4 are prevalent in any one ethnic group. The condition is autosomal dominant, which typically requires at least one affected parent.

Sources

NIH, Genetic Home Reference: KCNQ4 gene.

See http://ghr.nlm.nih.gov/gene/KCNQ4

NIH, Genetics Home Reference: Nonsyndromic deafness.

See http://ghr.nlm.nih.gov/condition/nonsyndromic-deafness

Smith, R.J.H. & Hilderbrand, M. (2008), “DFNA2 nonsyndromic hearing loss,” in Pagon, R.A. et al., editors, GeneReview [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1209/

PrevenTest looks at 36+ genes that are linked to 8+ hereditary cancers. These cancers are Breast, Ovarian, Colorectal, Endometrial, Melanoma, Pancreatic, Gastric, Prostate, and other less common cancers.

Cystic Fibrosis is caused by defects in the CFTR gene. However, defects in the CA12 gene can lead to individuals with high sweat chloride concentrations. Such high levels are normally indicative of cystic fibrosis, but in these cases the other symptoms of classical cystic fibrosis are not present: there is no evidence of lung disease or poor pancreatic function leading to digestive problems. Usually males with classical cystic fibrosis are sterile, but since the CA12 related condition has mainly been described in children, it’s not clear whether it’s normally associated with male sterility. The CA12 gene encodes for the carbonic anhydrase 12 enzyme. Children with the condition had low levels of sodium (hyponatremia), high levels of potassium (hyperkalemia), suffered from dehydration, and failed to thrive in the first year. Normal growth usually resumes after one year of age. Elevated sweat chloride levels from mutations in the CA12 gene is an extremely rare disease. Initial studies focused on a group of related Bedouin in Israel, but it is not known if the condition is more common in any particular ethnic group. The condition is autosomal recessive, which typically requires an affected child to have two asymptomatic carrier parents.

Sources

Feldshtein, M. et al. (2010), “Hyperchlorhidrosis Caused by Homozygous Mutation in CA12, Encoding Carbonic Anhydrase XII,” American Journal of Human Genetics, 87, 713-720.

See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2978943/

John Hopkins Website: CF and CF-Related Disorders.

See http://www.hopkinsmedicine.org/dnadiagnostic/CF_CFRelated_Panel.htm

Muhammed, E. et al. (2011), “Autosomal recessive hyponatremia due to isolated salt wasting in sweat associated with a mutation in the active site of Carbonic Anhydrase 12,” Human Genetics,129, 397-405.

See http://link.springer.com/article/10.1007%2Fs00439-010-0930-4

NIH, Genetic Home Reference: CA12 gene.

See http://ghr.nlm.nih.gov/gene/CA12

NIH, Genetics Home Reference: Cystic Fibrosis.

See http://ghr.nlm.nih.gov/condition/cystic-fibrosis

DNA sequence information is important because it may be an indicator/predictor of future disease, or a disease may be passed on to future children. Prior knowledge of future disease risk or risk for children to inherit a disease may influence the decisions made by you or your doctor. For example, a couple at serious risk to have a child inherit a fatal disease may opt, armed with the knowledge taken from their DNA sequences, to undergo in-vitro fertilization to prevent the birth of a child with a fatal genetic disease. Without the crucial information provided by DNA sequencing, the couple may not have been aware of their risk to have a child with a fatal disease, which may have affected their original reproductive decisions.

Maple syrup urine disease (MSUD) can be caused by mutations in a number of different genes, including the DLD gene. The DLD gene encodes for the enzyme dihydrolipoamide dehydrogenase. This enzyme is involved in a number of different enzyme complexes, including branched-chain alpha-keto acid dehydrogenase (BCKD), which is essential for the breakdown of branched chain amino-acids (leucine, isoleucine, and valine). Maple syrup urine disease is named due the sweet “maple syrup” smell from the urine of those with the disease, although the odor is seldom present in the type 3 disease. In the more common form of MSUD, untreated babies suffer from poor feeding and vomiting, followed by poor breathing, lethargy, and seizures. Death normally occurs within a few weeks of birth, but can be avoided by special formula milk, etc. As they grow up, those with the condition tend to suffer from movement disorders, such as tremors, and various mental problems, such as ADHD, low intelligence, autism, depression, and anxiety. However, in type 3 of maple syrup disease, many other symptoms can be present, since the dihydrolipoamide dehydrogenase enzyme is a component of other enzyme complexes, such as the pyruvate dehydrogenase complex. Lactic acidosis is common in infants with the type 3 disease, giving rise to muscle weakness and lethargy. Type 3 MSUD is vary variable, and in some cases the symptoms of the most common form of MSUD are absent, or their onset delayed. The disease is often episodic, worsening when the body is stressed by an infection, etc. Adult-onset liver disease can occur, which is not a normal symptom of MSUD. All types of Maple syrup urine disease occur in about 1 in 185,000 live births worldwide. Type 3 MSUD is extremely rare, but is most commonly seen in those of Ashkenazi Jewish descent, where it affects about 1 in 40,000 individuals. The faulty gene is inherited in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers.

Sources

NIH, Genetics Home Reference: Dihydrolipoamide dehydrogenase deficiency.

See http://ghr.nlm.nih.gov/condition/dihydrolipoamide-dehydrogenase-deficiency

NIH, Genetics Home Reference: DLD gene.

See http://ghr.nlm.nih.gov/gene/DLD

NIH, Genetics Home Reference: Maple syrup urine disease.

See http://ghr.nlm.nih.gov/condition/maple-syrup-urine-disease

Quinonez, S.C. & Thoene, J.G. (2014), “Dihydrolipoamide dehydrogenase deficiency,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK220444/

Strauss, K.A. et al. (2006), “Maple Syrup Urine Disease,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1319/

NewbornGeneID detects gene mutations (defects in the genes) linked to many of the most common and devastating diseases that can be passed unknowingly from parent to child. Newborn screening is a test for parents and prospective parents that provides information on whether a patient has a gene mutation(s) that are linked to a disease. The results provide information on the likelihood that a child will inherit one of a number of rare diseases.

Phenylketonuria (PKU) is caused by mutations in the PAH gene. This gene encodes for the enzyme phenylalanine hydroxylase, which breaks down the amino acid phenylalanine. The buildup of phenylalanine causes damage to the body, affecting mainly the brain. If left untreated, those with phenylketonuria suffer from intellectual disability, seizures, delayed development, and psychiatric problems. A musty odor from phenylalanine may be evident. Treatment is by a special low phenylalanine diet, which can allow for normal development if strictly adhered to. There are rarer, less damaging forms of the disease, known as non-PKU hyperphenylalaninemia. Phenylketonuria is found in 1 in 10,000 to 1 in 15,000 new births. Since screening and prompt treatment are almost universal in the USA, the symptoms are very rarely seen. The disease is more common in some ethnic groups, such as Turks (1 in 2,600 births) and Irish (1 in 4,600 births). The condition follows an autosomal recessive pattern, typically requiring both parents to be carriers asymptomatically.

Sources

Mitchell, J.J. (2000), “Phenylalanine hydroxylase deficiency,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1504/

NIH, Genetic Home Reference: PAH gene.

See http://ghr.nlm.nih.gov/gene/PAH

NIH, Genetics Home Reference: Phenylketonuria.

See http://ghr.nlm.nih.gov/condition/phenylketonuria

Recombine Website. Phenylalanine Hydroxylase Deficiency.

See https://recombine.com/diseases/phenylalanine-hydroxylase-deficiency

Pendred syndrome is a syndromic condition that involves deafness and the formation of a goiter on the thyroid gland. The gene SLC26A4 encodes a protein called pendrin, which is involved in anion transport. It is found in the thyroid (where it is believed to be involved in iodide ion transport), kidney, and inner ear. Those born with Pendred syndrome are normally deaf at birth, although in some cases deafness arrives during early childhood. A goiter is normally seen during adolescence or early adulthood. In some cases SLC26A4 defects cause deafness without any other symptoms, known as non-syndromic hearing loss, or DFNB4 deafness. The exact occurrence of Pendred syndrome is not known, although one estimate calculated that 7.5% of all congenital deafness are due to the syndrome. It is not clear whether some ethnic groups are more affected than others. The condition is autosomal recessive, which typically occurs when both parents of an affected child are asymptomatic carriers.

Sources

Alasti, F. et al. (1998), “Pendred Syndrome / DFNB4”. In Payon R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1467/

NIH, Genetic Home Reference: SLC26A4 gene.

See http://ghr.nlm.nih.gov/gene/SLC26A4

NIH, Genetics Home Reference: Pendred syndrome.

See http://ghr.nlm.nih.gov/condition/pendred-syndrome

If your test returns a positive result, it means that we identified a mutation that increases the risk of cancer. The key to proper management of your test results is first to understand the information provided in your report. With this information at hand, you can then fully understand your cancer risk and create a manageable plan to curtail that risk. GeneID’s report will guide you by explaining the genes, diseases or cancers in question, the general and reproductive recommendations, as well as the potential risks to family members, to achieve a holistic perspective of your and your family’s risk.

A positive result on a GeneID Cancer Genetics Panel means that you inherited a faulty gene from either one or both of your parents. This faulty gene, or mutation, increases your risk for one or several types of cancers.

It is important to distinguish between having a mutation and having cancer: if you test positive for a mutation, that does not mean that you have cancer, nor does it mean that you definitely will get cancer.

Risk and Management:

You may have been prompted to take a cancer genetic test after discovering a family history of cancer. Alternatively, you may have had cancer already and want to understand your risk of the cancer returning, or the chance of developing other cancer types. Family history or personal cancer history may increase your cancer risk compared to the general population.

Your testing report provides you information regarding the cancers related to your potential gene mutation. Once you have the results, you can mitigate your cancer risk with several options:

• Increased screening to catch any potential cancers in their initial stages

• Certain medications may be prescribed depending on the relevant condition

• Lifestyle changes, including diet and exercise

• Surgery

Together with your healthcare provider, one or several of these options may be discussed and implemented to personalize your prevention or treatment.

Family:

Since your results may affect the health of other family members, it is important to discuss and share your results with them. They may decide to consult their healthcare providers to see how your results might affect them, including the option for genetic testing.

Spinal muscular atrophy (SMA) can be caused by mutations in a number of genes, usually the SMN1 gene. However, in a few cases SMA is caused by mutations in the DYNC1H1 gene. This gene encodes for a protein that is part of a motor protein complex called dynein. If dynein is ineffective in moving proteins and other materials around cells, the motor neurons in the spinal cord may not function properly. The SMA caused by the DYNC1H1 gene causes muscle weakness only in the lower limbs, particularly the thigh muscles, so is referred to as spinal muscular atrophy, lower extremity, dominant (SMA-LED). Sufferers find it difficult to climb stairs, get up from a chair, or walk long distances. The disease normally first occurs in childhood, but is not life-threatening. SMA caused by SMN1 defects is divided into different types; types 1-4 of SMA all involve muscle weakness. Type 1 SMA first occurs before 6 months. Affected babies are unable to hold their heads up or sit up. They typically have difficulty swallowing and breathing, and tend not to survive beyond the age of two. Type 2 SMA first occurs between 6 months and a year. Babies can sit up, but do not go on to stand or walk unaided in the usual manner. Type 3 SMA first occurs in older children. They can normally walk unaided, but may find climbing stairs or other similar tasks difficult. They may need to use a wheelchair by mid-life. Type 4 SMA first occurs in adulthood. Sufferers have some muscle weakness, tremors, and mild breathing problems. The incidence of spinal muscular atrophy (all types) is around 1 in 6,000 to 1 in 10,000 births. However, SMA from DYNC1H1 mutations only affects a small number of families. Unlike SMN1 defects, which are autosomal recessive, the mutations in DYNC1H1 are autosomal dominant. Typically, autosomal dominant inheritance require at least one affected parent.

Sources

NIH, Genetics Home Reference: DYNC1H1 gene.

See http://ghr.nlm.nih.gov/gene/DYNC1H1

NIH, Genetics Home Reference: Spinal Muscular Atrophy.

See http://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy

Harms, M.B. et al. (2010), “Dominant spinal muscle atrophy with lower extremity predominance,” Neurology, 75, 539-546.

See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918478/

Long QT syndrome 11 (LQT11) is a heart condition caused by defects in the “A kinase anchor protein 9,” or AKAP9 gene, which encodes for protein AKAP9. It is involved in the anchoring of the protein kinase A enzyme complex in the cell and other cellular functions. In the heart, protein kinase A is involved in the activation of various ion channel proteins through phosphorylation, which are important for maintaining a regular heartbeat. Long QT refers to the abnormal signal on an electrocardiogram (ECG) seen with LQT patients. Such patients are at risk of episodes of increased heart rate, known as torsades de point, which may result in fainting or cardiac arrest. Death can sometimes occur, even in young people, so it is important that any fainting episodes are properly investigated. Treatment is by means of beta-blockers or implantable cardioverter-defibrillators (ICDs). Long QT syndrome types such as this, which only affect the heart, are also known as Romano-Ward syndrome. Overall, it’s estimated that about 1 in 2000 people, or 150,000 cases, suffer from LQT, some without knowing it. The condition does not seem to be more prevalent in any ethnic group. The affected gene is inherited in an autosomal dominant manner, which normally is inherited from one parent who also has the condition.

Sources

Alders, M. & Christiaans, I. (2003), “Long QT syndrome,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1129/

Chen, L. et al. (2007), “Mutation of an A-kinase-anchoring protein causes long-QT syndrome,” Proc. Acad. Natl. Sci. U.S.A.,” 104, 20990 – 20995.

See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409254/

NIH, Genetics Home Reference: AKAP9 gene.

See http://ghr.nlm.nih.gov/gene/AKAP9

NIH, Genetics Home Reference: Romano-Ward Syndrome.

See http://ghr.nlm.nih.gov/condition/romano-ward-syndrome

Usher syndrome is a condition that involves various degrees of deafness and gradual impairment of vision. Those with Usher syndrome type 1 are usually born deaf, and begin to lose vision while still children. A number of different genetic mutations can cause Usher syndrome type 1, including mutations in the CDH23 gene (Usher syndrome type 1D). CDH23 encodes for the protein cadherin 23, which is involved in cell aggregation, including aggregation in the retina and ear. The vision loss from Usher’s syndrome is due to the condition retinitis pigmentosa, which involves the gradual deterioration of retinal rod photoreceptor cells (leading to night blindness), followed by cone receptor cells (leading eventually to complete blindness). In addition to deafness, Usher syndrome type 1 affects the ability to balance. Children with the condition are typically slow to stand up and walk. The prevalence of Usher syndrome type 1 in the USA is over 4 in 100,000. The number due to CDH23 mutations is relatively low. In a survey of 34 families with members affected by Usher syndrome type 1, only 6 were affected by defects in the CDH23 gene. Usher syndrome type 1 is more common in certain ethnic groups, such as Ashkenazi Jews and the Acadians (Cajuns) of Louisiana. The condition is autosomal recessive, so typically an affected child will have two asymptomatic carrier parents.

Sources

NIH, Genetic Home Reference: CDH23 gene.

See http://ghr.nlm.nih.gov/gene/CDH23

NIH, Genetics Home Reference: Usher syndrome.

See http://ghr.nlm.nih.gov/condition/usher-syndrome

Roux, A.-F. et al. (2006), “Survey of the frequency of USH1 gene mutations in a cohort of Usher patients shows the importance of cadherin 23 and protocadherin 15 genes and establishes a detection rate of above 90%,” Journal of Medical Genetics, 43, 763-768.

See http://jmg.bmj.com/content/43/9/763.abstract

Familial thoracic aortic aneurysm and dissection, or familial TAAD, can be caused by defects in the MYH11 gene. The gene encodes for the myosin-11 protein, a contractile protein in smooth muscle. Cases of familial TAAD caused by defects in MYH11 are often associated with the condition Patent ductus arteriosus, or PDA, a congenital heart defect. The overall incidence of familial TAAD caused by MYH11 is low, accounting for only 1% of the total incidence of familial TAAD, which is itself only involved in around 20% of all cases of TAAD.

Sources

Pannu H1, Tran-Fadulu V, et al. MYH11 mutations result in a distinct vascular pathology driven by insulin-like growth factor 1 and angiotensin II. Hum Mol Genet. 2007 Oct 15;16(20): 2453-62

See https://www.ncbi.nlm.nih.gov/pubmed/?term=17666408

Alpha Thalassemia, Aortic Dysfunctions, Beta Thalassemia, Bloom Disease, Canavan Disease, Cystic Fibrosis and CF related diseases, Familial Dysautonomia, Fanconi Anemia, Fragile-X, Galactosemia, Gaucher Disease, Glycogen Storage Disease Type IV, Long Q-T Syndrome, Maple Syrup Disease, Mucolipidosis Type IV, Niemann Pick Disease, Non-Syndromic Hearing Loss, OTC Deficiency, Phenylketonuria, Pompe Disease (Glycogen Storage Disease Type 2), Sickle Cell Disease (Anemia), Spinal Muscular Atrophy, Tay-Sachs and Usher Syndrome within others.

Familial thoracic aortic aneurysm and dissection, or familial TAAD, can be caused by defects in the MYLK gene. The gene encodes for the myosin light chain kinase protein found in smooth muscles. In patients with TAAD, the aorta increases in diameter, and dissection (blood flowing through the artery wall, following a tear) may occur at some point. In cases of TAAD caused by MYLK gene defects, it appears that dissection may occur without significant widening of the aorta. Rupture of the artery can follow, often leading to rapid death. Surgery is often required where a significant thoracic aortic aneurysm occurs. With proper management, life expectancy for those with familial TAAD can approach that of the general population. The incidence of familial TAAD caused by MYLK is low, accounting for only 1% of the total incidence of familial TAAD. Overall, familial TAAD is estimated to cause roughly 20% of thoracic aortic aneurysms and dissections. Approximately 10,000 deaths per year occur due to TAAD in the USA, so about 2,000 will be due to familial TAAD, giving around 20 deaths per year from MYKL defects, out of an overall USA total of around 2.6 million (0.001% of total deaths).

Sources

Centers for disease control and prevention, “Deaths: Final Data for 2013.”

See http://www.cdc.gov/nchs/fastats/deaths.htm

Milewicz, D.M. & Regalado, M., Thoracic Aortic Aneurysms and Aortic Dissections, (2003), Feb.13th, in Pagon, R.A. et al, editors. Genereviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1120/

NIH, Genetics Home Reference: Familial TAAD.

See http://ghr.nlm.nih.gov/condition/familial-thoracic-aortic-aneurysm-and-dissection

Wang, L. et al. (2010), “Mutations in myosin light chain kinase cause familial aortic dissections,”Am.J.Hum.Genet.,87,701-707.

See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2978973/

Glycogen storage disease II, also known as Pompe disease, is caused by mutations in the GAA gene. This gene encodes for the enzyme alpha-glucosidase, which breaks down glycogen into glucose. Without this enzyme, glycogen can build up to toxic levels, damaging muscles, including the heart muscles, as well as an inability to maintain normal fasting glucose levels. The classic form of the disease emerges in the first few months of life. Babies exhibit muscle weakness, breathing difficulties, heart problems, and fail to thrive. Mortality rates are high, few surviving the first year without treatment. A “non-classic” infantile form appears in the first year of life. Symptoms are similar, but the heart tends to be less severely affected. Even so, breathing difficulties mean that few survive for more than a few years without treatment. A late-onset form of the disease is also known, in which symptoms first appear during late childhood, adolescence, or adulthood. Here muscle weakness and respiratory problems arise, but usually the heart is unaffected. Most sufferers from this form die within 30 years of diagnosis without treatment. Enzyme replacement therapy, along with treatment for the various symptoms, can extend survival to some extent. The incidence of glycogen storage disease type II is around 1 in 40,000 in the USA, rising to 1 in 14,000 among African Americans. The carrier rate reaches about 1 in 60 in the latter population. The defective genes are inherited in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers for the faulty gene.

Sources

Leslie, N. & Tinkle, B.T. (2007), “Glycogen Storage Disease Type II (Pompe Disease),” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1261/

NIH, Genetics Home Reference: GAA gene.

See http://ghr.nlm.nih.gov/gene/GAA

NIH, Genetics Home Reference: Pompe Disease.

See http://ghr.nlm.nih.gov/condition/pompe-disease

Recombine Website: Glycogen Storage Disease, Type 2.

See https://recombine.com/diseases/glycogen-storage-disease-type-ii

After receiving genetic testing, it is recommended that you speak to a genetic counselor to best understand the impact of the test results. If you test positive for a hereditary cancer syndrome, it does not mean that you have cancer or that you will get cancer. Your provider can help you learn what preventative options you can take based on the risks associated to your cancer.

Arterial tortuosity syndrome (ATS) is caused by mutations in the SLC2A10 gene. The gene encodes for the protein GLUT10, which is believed to help regulate cell proliferation. Those with the syndrome have unusually long, often twisted, arteries which are prone to aneurysm (bulging), stenosis (constriction), and dissection (blood flowing through the torn artery wall). Arterial rupture, or constriction of the blood supply to vital organs, can lead to early mortality. Many sufferers die as children, although others may survive longer. Other symptoms of the syndrome include: elastic skin, very mobile or restricted joints, and various hernias. Sufferers tend to have elongated faces, widely spaced eyes (hypertelorism), and small chins. Arterial tortuosity syndrome is an extremely rare condition: only about 100 cases have been reported worldwide. The genetic abnormality is recessive, requiring one faulty gene from each parent. No evidence has shown more prevalence in any particular ethnic group.

Sources

Faiyz-Ul-Haque, M., et al. (2008), “Identification of a p.Ser81Arg encoding mutation in SLC2A10 gene of arterial tortuosity syndrome patients from 10 Qatari families,” Clinical Genetics, 74, 189-193.

See http://onlinelibrary.wiley.com/doi/10.1111/j.1399-0004.2008.01049.x/abstract-NIH

Genetics Home Reference: Arterial Tortuosity Syndrome.

See http://ghr.nlm.nih.gov/condition/arterial-tortuosity-syndrome

Nord Website, Arterial Tortuosity Syndrome.

See https://rarediseases.org/rarediseases/arterial-tortuosity-syndrome/

Understanding Negative Results

If your test returns a negative result, it means that there are no known mutations in your genes that are associated with higher risks for cancer. For this reason, you are at a significantly lower risk for developing a hereditary cancer. However, the possibility for cancer is not completely eliminated.

In some cases, cancer may be present in a family without any known genetic reason for hereditary cancer. If this is relevant to your family, you may still be at risk. In consult with your healthcare provider, you may want to consider increasing your rate of cancer screenings to closely monitor areas that your history may dictate has an elevated cancer risk.

There are two types of negative results:

True-negative - The person is not a carrier of a known cancer-predisposing gene that has been positively identified in another family.

Indeterminate - The person is not a carrier of a known cancer-predisposing gene, and the carrier status of other family members is either also negative or unknown.

Risk and Management:

You may have been prompted to take a cancer genetic test after discovering a family history of cancer. Alternatively, you may have had cancer already and want to understand your risk of the cancer returning, or the chance of developing other cancer types. Family history or personal cancer history may increase your cancer risk compared to the general population.

Your testing report provides you information regarding the cancers related to your potential gene mutation. Once you have the results, you can mitigate your cancer risk with several options:

• Increased screening to catch any potential cancers in their initial stages

• Certain medications may be prescribed depending on the relevant condition

• Lifestyle changes, including diet and exercise

• Surgery

Together with your healthcare provider, one or several of these options may be discussed and implemented to personalize your prevention or treatment.

Family:

Since your results may affect the health of other family members, it is important to discuss and share your results with them. They may decide to consult their healthcare providers to see how your results might affect them, including the option for genetic testing.

A genetic disease is a disease that is caused because of a mutation in an individual’s genetics. When this mutation is passed from parent to child, it is considered hereditary.

Bloom syndrome is caused by mutations in the BLM gene, which encodes for one of the RecQ helicase proteins. These proteins have an important role in preserving the integrity of DNA, as well as catalyzing key reactions that are crucial for DNA unwinding. Those with the disease have unusually short stature, and are very sensitive to sunlight, often having reddish marks on their faces. Men are sterile, while women have reduced fertility with an early onset of menopause. Most sufferers are of normal intellectual ability, although some suffer from learning difficulties. Cancer is much more likely in those with Bloom syndrome, often first appearing in their 20s or 30s. Early mortality from cancer is common, although sufferers often respond successfully to treatment. Bloom disease is an extremely rare condition, with about 300 cases known worldwide, about a quarter of which are among those Ashkenazi Jewish descent. The condition is autosomal recessive, which typically requires an affected child to have two asymptomatic carrier parents.

Sources

NIH, Genetics Home Reference: BLM gene.

See http://ghr.nlm.nih.gov/gene/BLM

NIH, Genetics Home Reference: Bloom Syndrome.

See http://ghr.nlm.nih.gov/condition/bloom-syndrome

Sanz, M. M. & German, J., (2006), “Bloom’s Syndrome,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1398/

Recombine Website. Bloom Syndrome.

See https://recombine.com/diseases/bloomsyndrome

Loeys-Dietz Syndrome Type I is caused by mutations in the TGFBR1 gene. Other types of the syndrome are caused by faults in other genes. The TGFBR1 gene encodes the production of the TGF-β receptor 1 protein, which is believed to be involved in regulating cell proliferation. Those with the syndrome are liable to arterial aneurysms and tortuosity, along with hypertelorism (large distance between the eyes), cleft palates, and bifid (split) uvulae. Early mortality can occur due to arterial rupture. Loeys-Dietz Syndrome Type I is a rare condition, only found so far in a fairly small number of families. It is not yet possible to estimate its overall prevalence, or whether it is more common in particular ethnic groups. The Type 1 syndrome is believed to be the most common form of Loeys-Deitz syndrome. The defective gene is autosomal dominant, typically requiring at least one affected parent.

Sources

NIH, Genetics Home Reference: Loeys-Dietz Syndrome.

See http://ghr.nlm.nih.gov/condition/loeys-dietz-syndrome

NIH, Genetics Home Reference: TGFBR1.

See http://ghr.nlm.nih.gov/gene/TGFBR1

OMIM, Loeys-Dietz Sydrome 1.

See https://omim.org/entry/609192

Most people are born with 46 chromosomes. Chromosomes contain genes, which is where our DNA is. DNA is the “instructional manual” of the body. These 46 chromosomes are made of 23 pairs of chromosomes. We get one chromosome from each of our parents. This means that for each trait in our body (with rare exceptions) we have 2 chromosomes that determine what that trait will be.

In general, even if a person has different genes for a specific trait, only one of the genes will be visible. For example, if an individual has one gene for brown eyes and one for blue eyes, they will not have one brown eye and one blue eye. Instead they will have two brown eyes. This is because the gene for the color brown is “dominant.” Traits that are not dominant are called “recessive.” A recessive trait will only be apparent if the individual has two copies of that trait.

An exception to the rule above are traits known as “X-linked” traits. These traits are linked to the X chromosome. Females have two X chromosomes while males have one X chromosome and one Y chromosome. This means that males do not have one section of gene (the second leg of the “X”). For recessive traits that are on this gene, females, who have 2 “X” genes, will require two mutated genes; by contrast, males, who receive a “Y” gene from their Dad, will have the disease if they inherit a mutated gene from their mother. For this reason, “X-Linked recessive disorders” are much more common amongst men than they are in women. Examples of X-linked recessive disorders include Hemophilia A and Red-green color blindness.

Alpha Thalassemia is caused by defects in the HBA1 or HBA2 genes. These genes encode for the protein alpha-globin, a component of hemoglobin. There are two forms of the disease: Hb Bart syndrome and HbH disease. The former is more severe, affecting unborn babies. They suffer from general edema (swelling from fluid buildup), anemia, heart defects, and enlargement of the liver and spleen. Most are stillborn, or die within a few days of birth. Carrying an Hb Bart fetus may be harmful to the mother. HbH disease involves moderate anemia, jaundice, and enlargement of the liver and spleen. Abnormal skeletal changes are sometimes seen. Symptoms may begin in either childhood or adulthood. Generally, those with HbH can live a near-normal lifespan, although some may need blood transfusions if anemia becomes severe. The inheritance of the faulty genes is complex, but involves a number of categories of both carriers and those with symptoms. The disease is relatively common, particularly in South-East Asia. Other regions badly affected include India, the Middle East, Africa, and Mediterranean countries. Worldwide, about 1 in 48 people are carriers for the condition.

Sources

NIH, Genetics Home Reference: HBA1 gene.

See http://ghr.nlm.nih.gov/gene/HBA1

NIH, Genetics Home Reference: HBA2 gene.

See http://ghr.nlm.nih.gov/gene/HBA2

NIH, Genetics Home Reference: Alpha-thalassemia.

See http://ghr.nlm.nih.gov/condition/alpha-thalassemia

Origa, R. et al. (2005), “Alpha-Thalassemia,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1435/

Recombine Website. Alpha-thalassemia.

See https://recombine.com/diseases/alphathalassemia

There are many reasons people get tested.

Patients with cancer or a history of cancer can use genetic testing to see if specialized and potentially more effective treatment options are available for them. These patients may also want to know if they are at increased risk for developing other "linked" cancers. Additionally, patients may want to know if their family members are at similar lifetime risk.

Patients without cancer, but with a family history of cancer, may want to get tested to see if they are at increased risk of developing cancer. This can help physicians create a personalized prevention plan.

The odds of being a carrier depend on the type of the disease and the individual’s ethnicity. In some studies, the incidence of testing positive as a carrier is as high as 25% or more when testing for a number of diseases at once. For cystic fibrosis, one of the more common diseases, the rates are:

Table 1. Cystic Fibrosis Detection and Carrier Rates Before and After Testing

Racial or Detection Carrier Risk Approximate Carrier Risk Ethnic Group Rate* (%) Before Testing After Test Negative Result† Ashkenazi Jewish 94 1/24 1/380

Non-Hispanic White 88 1/25 1/200

Hispanic White 72 1/58 1/200

African American 64 1/61 1/170

Asian American 49 1/94 1/180

*Detection rate data based on the use of a 23-mutation panel.

†Bayesian statistics used to calculate approximate carrier risk after a negative test result.

Modified from the American College of Medical Genetics. Technical Standards and Guidelines for CFTR Mutation Testing, 2006 Edition. Available at: http://www.acmg.net/Pages/ACMG_Activities/stds-2002/cf.htm. Retrieved December 16, 2010.

Genetic testing is generally done only once as genetics rarely change. A doctor might recommend testing for genes that were not previously tested for.

Beta Thalassemia is caused by mutations in the HBB gene, which encodes for the protein beta-globin, a subunit of hemoglobin. There are two forms of the disease, beta thalassemia major and beta thalassemia intermedia, the latter being less severe. With beta thalassemia major, symptoms develop before the age of two. Severe anemia is common, necessitating frequent blood transfusions. Other symptoms include jaundice, skeletal defects, and enlargement of the heart, liver, and spleen. Delayed adolescence may occur. Over time, excess iron from transfusions builds up in the body, and needs to be removed by chelation drugs. Premature death from cardiac mortality is common, but decreasing as treatments improve. Thalassemia intermedia is associated with mild anemia, some skeletal abnormalities, and in some cases growth inhibition. The worldwide incidence of beta-thalassemia is 1 in 100,000 new births. Regions with high levels of the disease include Mediterranean countries, the Middle-East, Central Asia, Africa, and the Far East. In the USA, those whose ancestors came from these regions have a higher risk of the disease than other ethnic groups. The mutated gene is inherited in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers of the faulty gene copy.

Sources

NIH, Genetics Home Reference: HBB gene.

See http://ghr.nlm.nih.gov/gene/HBB

NIH, Genetics Home Reference: Beta-thalassemia.

See http://ghr.nlm.nih.gov/condition/beta-thalassemia

Origa, R. (2000), “Beta-Thalassemia,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1426/

Recombine Website. Beta-thalassemia.

See https://recombine.com/diseases/betathalassemia

Familial Thoracic Aortic Aneurysm and Dissection (Familial TAAD) and Loeys-Dietz Syndrome Type II can both be caused by different mutations in the TGFBR2 gene. The TGFBR2 gene encodes for the TGF-β receptor type 2, which is believed to be involved in the regulation of cell proliferation. Other types of Loeys-Dietz syndrome are caused by faults in other genes. Those with the syndrome are liable to arterial aneurysms and tortuosity, along with hypertelorism (large distance between the eyes), cleft palates, and bifid (split) uvulae. It is estimated that about 4% of the total cases of familial TAAD are due to mutations in the TGFBR2 gene. In patients with TAAD, the aorta increases in diameter, and dissection (blood flowing through the artery wall, following a tear) may occur at some point. Rupture of the artery may follow, often leading to rapid death. Surgery is often required where a significant thoracic aortic aneurysm occurs. With proper management, life expectancy for those with familial TAAD can approach that of the general population. The two conditions are separate: familial TAAD doesn’t give rise to the other symptoms seen with Loeys-Dietz Syndrome Type II. Loeys-Dietz Syndrome Type II is a very rare condition, only found so far in a fairly small number of families. It is not yet possible to estimate its overall prevalence, or whether it is more common in particular ethnic groups. The defective gene is autosomal dominant, typically requiring at least one affected parent. Familial TAAD comprises about 20% of the overall cases of TAAD. About 10,000 people in the USA die each year from TAAD, so around 2,000 of these will be due to familial TAAD, hence there are roughly 80 deaths per year from TAAD from TGFBR2 defects.

Sources

Centers for disease control and prevention, “Deaths: Final Data for 2013.”

See http://www.cdc.gov/nchs/fastats/deaths.htm

Milewicz, D.M. & Regalado, M., Thoracic Aortic Aneurysms and Aortic Dissections, (2003), Feb.13th, in Pagon, R.A. et al, editors. Genereviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1120/

NIH, Genetics Home Reference: Familial TAAD.

See http://ghr.nlm.nih.gov/condition/familial-thoracic-aortic-aneurysm-and-dissection

NIH, Genetics Home Reference: Loeys-Dietz Syndrome.

See http://ghr.nlm.nih.gov/condition/loeys-dietz-syndrome

NIH, Genetics Home Reference: TGFBR2 gene.

See http://ghr.nlm.nih.gov/gene/TGFBR2

Testing positive means that you are a carrier for a specific disease, in other words, you have a single faulty copy of the gene. It does not mean that you have the disease, nor does it mean that your children will have the disease. If your partner is also a carrier of a positive mutation for the same gene (even if it is a different mutation) any offspring are at a 1 in 4 risk of inheriting the disease.

Mucolipidosis type IV is a disease caused by defects in the MCOLN1 gene, which encodes for the protein mucolipin 1. This protein is found in the membranes of lysosomes and endosomes, and is involved in the transport of various molecules. Mucolipin 1 is essential for the development and maintenance of the brain and retina. Infants with the disease typically develop poor motor skills, being slow to crawl, and rarely learning to walk or speak properly. Sufferers may have muscle weakness and difficulties swallowing. Visual impairment gradually advances, usually leading to complete blindness before the age of 10. Iron deficiency may occur as well. A small number of sufferers, about 5% of the total, develop a milder form of the disease, where they may be able to walk and talk. People with mucolipidosis type IV may live for many decades, although they tend to have a shortened lifespan. Overall, it’s estimated that about 1 in 625,000 people suffer from mucolipidosis type IV, although the figure rises to 1 in 37,000 among those of Ashkenazi Jewish descent, where about 1 in 100 may be carriers. The faulty gene is inherited in an autosomal recessive manner, which typically requires both parents to be asymptomatic carriers of the faulty gene copy.

Sources

NIH, Genetics Home Reference: MCOLN1 gene.

See http://ghr.nlm.nih.gov/gene/MCOLN1

NIH, Genetics Home Reference: Mucolipidosis Type IV.

See http://ghr.nlm.nih.gov/condition/mucolipidosis-type-iv

Recombine Website: Mucolipidosis Type IV.

See https://recombine.com/diseases/mucolipidosis-type-iv

Schiffmann, R. et al. (2005), “Mucolipidosis IV,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1214/

Cancer testing is requested through your doctor. If your office is interested in testing and does not have kits, they can contact us at 201-825-0186 or email at shipping@geneidlab.com

Familial dysautonomia is caused by defects in the IKBKAP gene. This gene encodes for a protein called IKK complex-associated protein, which plays a role in protein transcription. Nerve cells are adversely affected when the protein fails to function. Children with the disease typically suffer from gastrointestinal problems (such as vomiting), feeding difficulties, somewhat stunted growth, muscle weakness, and a lack of sensitivity to pain or temperature. Sufferers are liable to suffer from lung infections far more than normal. Curvature of the spine and deterioration in vision often occur. Walking becomes increasingly difficult as adulthood is reached, and many patients reach the point where they are no longer able to walk unaided. Kidney damage is also common during adulthood. Early death is likely, often due to lung infections, although improvements to treatment mean that around half of all patients now survive to age 40. Familial Dysautonomia is normally found in those of Ashkenazi Jewish descent, where about 1 in 3,700 are affected; approximately 1 in 36 are carriers. The mutated gene is inherited in an autosomal recessive manner, which typically requires both parents to be asymptomatic carriers of the faulty gene copy. However, there have been cases of both male and female sufferers having children, although pregnancy is high risk for those with the condition. The offspring between affected patients and non-carriers will normally be asymptomatic carriers.

Sources

NIH, Genetics Home Reference: Familial Dysautonomia.

See http://ghr.nlm.nih.gov/condition/familial-dysautonomia

NIH, Genetics Home Reference: IKBKAP gene.

See http://ghr.nlm.nih.gov/gene/IKBKAP

Recombine Website: Familial Dysautonomia.

See https://recombine.com/diseases/familial-dysautonomia

Shohat, M. & Weisz Hubshman, M. (2003), “Familial Dysautonomia,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1180/

The DNA sample is collected using mouthwash. It is simple and non-invasive.

After getting genetic testing, it is recommended that you speak to a genetic counselor to best understand the impact of the test results. If you test positive for a disease it is important to test your partner to determine whether they are also a carrier. If you are pregnant you may want to test the child as well, although some of the diseases have no cure, (and the range of severity can vary amongst people with the same disease), so it is a personal decision.

Your doctor or a local genetic counselor should be able to provide more information about cancer testing. You can find a genetic counselor through the National Society of Genetic Counselors (www.nsgc.com.)

Glycogen storage disease II, also known as Pompe disease, is caused by mutations in the GAA gene. This gene encodes for the enzyme alpha-glucosidase, which breaks down glycogen into glucose. Without this enzyme, glycogen can build up to toxic levels, damaging muscles, including the heart muscles, as well as an inability to maintain normal fasting glucose levels. The classic form of the disease emerges in the first few months of life. Babies exhibit muscle weakness, breathing difficulties, heart problems, and fail to thrive. Mortality rates are high, few surviving the first year without treatment. A “non-classic” infantile form appears in the first year of life. Symptoms are similar, but the heart tends to be less severely affected. Even so, breathing difficulties mean that few survive for more than a few years without treatment. A late-onset form of the disease is also known, in which symptoms first appear during late childhood, adolescence, or adulthood. Here muscle weakness and respiratory problems arise, but usually the heart is unaffected. Most sufferers from this form die within 30 years of diagnosis without treatment. Enzyme replacement therapy, along with treatment for the various symptoms, can extend survival to some extent. The incidence of glycogen storage disease type II is around 1 in 40,000 in the USA, rising to 1 in 14,000 among African Americans. The carrier rate reaches about 1 in 60 in the latter population. The defective genes are inherited in an autosomal recessive manner, typically requiring both parents to be asymptomatic carriers for the faulty gene.

Sources

Leslie, N. & Tinkle, B.T. (2007), “Glycogen Storage Disease Type II (Pompe Disease),” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1261/

NIH, Genetics Home Reference: GAA gene.

See http://ghr.nlm.nih.gov/gene/GAA

NIH, Genetics Home Reference: Pompe Disease.

See http://ghr.nlm.nih.gov/condition/pompe-disease

Recombine Website: Glycogen Storage Disease, Type 2.

See https://recombine.com/diseases/glycogen-storage-disease-type-ii

Partners who are both carriers have a number of options that they may consider when looking to conceive. The decision regarding what steps to take is a personal one and can vary significantly based on the specific disease and personal factors related to the couple. Some people may decide not to do anything. That said, some of the options include:

Conceive naturally

Prenatal Screening

In vitro fertilization; testing the egg for genetic diseases before it is implanted

Using a sperm or egg donor who is not a carrier

Adoption

Choose not to have children

Classical galactosemia is caused by mutations in the GALT gene. This gene encodes for the enzyme galactose-1-phosphate uridyltransferase, which is one of the enzymes that break down galactose. If the enzyme fails to function, increasing amounts of galactose-1-phosphate build up in the body, causing damage to tissues. The symptoms usually appear in the first few days of life. Babies suffer from vomiting, diarrhea, liver damage, jaundice, and fail to thrive. They are more susceptible to infection from bacteria such as E. coli than normal. Untreated babies usually die, or have severe brain damage. Feeding babies from birth on lactose-free formula milk is necessary. As they get older, a special diet absent of galactose and lactose is necessary. Even so, treated children are still at risk of poor growth, eye and speech problems, and mild intellectual disability. Women tend to suffer from premature ovarian insufficiency, so may not be able to have children. A “clinical variant” galactosemia, with slightly milder symptoms and without the increased risk of bacterial infection, has been described. This is also caused by defects in the GALT gene. Other types of galactosemia are caused by defects in other genes. The incidence of classical galactosemia has been estimated as 1 in 10,000 to 1 in 48,000 in the general population. The disease is particularly common among Irish travelers and their descendants, where up to 1 in 14 may be carriers, compared to about 1 in 125 in the general population. The “clinical variant” form is mainly found in African Americans. The disease is autosomal recessive, typically requiring both parents to be asymptomatic carriers of the faulty gene. If a sufferer has children with a partner who is not a carrier for the disease, the children will be asymptomatic carriers.

Sources

Berry, G.T. (2000), “Classic Galactosemia and Clinical Variant Galactosemia,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK1518/

NIH, Genetics Home Reference: Galactosemia.

See http://ghr.nlm.nih.gov/condition/galactosemia

NIH, Genetics Home Reference: GALT gene.

See http://ghr.nlm.nih.gov/gene/GALT

Recombine Website: Classical Galactosemia.

See https://recombine.com/diseases/classical-galactosemia

In some cases, a parent may have a mutation for a disease, but the gene has incomplete penetrance and the disease does not occur until later in life, if at all. For this reason, it is important to test for certain diseases that are passed on in an autosomal dominant fashion, even though none of the parents show symptoms of the disease.

There are several reasons why many types of individuals should consider carrier testing:

The American College of Obstetricians and Gynecologists (ACOG) and the American College of Medical Genetics (ACMG) recommend offering screening for some genetic diseases to all patients who are considering having a child

Many ethnicities, including Caucasian, African American, Hispanic, Ashkenazi Jewish and others who are at increased risk for certain genetic diseases

Individuals with family members who have had an inherited disease, or have a known carrier mutation in the family, are at high risk of having a mutation

Egg or sperm donors may require carrier testing

Ornithine transcarbamylase deficiency is caused by mutations in the OTC gene. This gene encodes for the enzyme ornithine transcarbamylase, which carries out a key step in the urea cycle. The liver alters toxic ammonia and converts it to urea, a much safer is converted into urea, a much more neutral compound. If the enzyme is partially or wholly inactivated, damaging levels of ammonia will tend to build up in the body. The condition is much more common in males than females. Symptoms often occur within the first few days of life. They include poor feeding, muscle weakness, lethargy, seizures, and hyperventilation. Severe hypothermia and brain damage result if prompt treatment is not started. Dialysis and nitrogen scavenger compounds, such as sodium benzoate, can be used to remove ammonia from the body. Even when ammonia levels appear to be under control, a crisis can appear in which they become elevated again. Low protein diets are needed throughout life. Infants may even require a liver transplant. A late-onset form of the disease can commence later in life, sometimes triggered by injuries, operations, or starting a high protein diet. Typical symptoms include mental problems, headaches, and vomiting. The incidence of the disease is roughly 1 in 70,000 births, occurring in roughly 4,300 patients in the USA. There does not seem to be huge differences in its occurrence among different ethnic groups. The faulty gene resides on the X chromosome, also known as an X-linked disease. Unlike females, any male with the faulty gene will have the disease since males only have a single X chromosome. The severe version of the disease is very rare in females, since they would need two faulty genes, which is highly unlikely. Females with one faulty gene normally act as carriers with no symptoms, however 15% of them will show some symptoms during their lifetime. As the disease is linked to the X chromosome, affected fathers cannot pass it on to their sons. Their daughters of affected fathers will normally receive the faulty gene.. Mothers with the faulty gene, whether they are asymptomatic or not, have a 50% chance of passing it on to each child.

Sources

Lichter-Konecki, U. et al. (2013), “Ornithine Transcarbamylase Deficiency,” in Pagon, R.A. et al., editors, GeneReviews [Internet].

See http://www.ncbi.nlm.nih.gov/books/NBK154378/

NIH, Genetics Home Reference: Ornithine Transcarbamylase Deficiency.

See http://ghr.nlm.nih.gov/condition/ornithine-transcarbamylase-deficiency

NIH, Genetics Home Reference: OTC gene.

See http://ghr.nlm.nih.gov/gene/OTC

Recombine Website: Ornithine Transcarbamylase Deficiency.

See https://recombine.com/diseases/ornithine-transcarbamylase-deficiency

Even without any history of genetic disease in your family there are reasons to consider genetic testing. Although most hereditary diseases are fairly uncommon, approximately 80% of all recessive diseases occur in families with no known family history. This is because the diseases only occur when a person has two defective (mutated) genes, one from each of their parents. It is often the case that no one in the family had the disease for generations because individuals only had a single copy of the defective gene. People with one copy of the mutation are referred to as “carriers” for the specific disease. Although the parents themselves are healthy, they do “carry” a faulty gene and can pass it down to their children.

Carrier testing is generally only done once as genetics rarely change. A doctor might recommend testing for diseases that were not previously tested for.

Your doctor or a local genetic counselor should be able to provide more information about carrier testing. You can find a genetic counselor through the National Society of Genetic Counselors (www.nsgc.com.)

Carrier testing is requested through your doctor. If your office is interested in testing and does not have kits, they can contact us at 201-825-0186 or email at shipping@geneidlab.com

The DNA sample is collected using mouthwash and a cheek swab. It is simple and non-invasive.

Getting tested at the same time is not necessary, but will save time if one of the partners is a carrier for a disease. Often the female partner will get tested first, and the male partner will get screened if she tests positive for a disease, although either partner can be tested independently.

NewbornGene ID offers 2 testing options:

• NewBornGene Panel - 62 genes covering 24 different types of conditions (testing covers many different types of conditions, for example there are multiple types of Usher Syndrome tested for)

• Cystic Fibrosis Screen

The explanation of benefits is a statement of charges created by your insurance company. The information included usually has the details of the services performed, the provider's charges, and how the charges are being processed by your insurance company. This information is an explanation for the patient and should not be confused with a bill.

Most in-network patients have little to no out of pocket costs associated with genetic testing. Talk to your physician to see if your insurance covers genetic testing.

Yes! GeneID offers a private pay option for individuals that are out of network or do not currently have health insurance. Call us at 1-866-436-3263 to learn more about our private pay and payment plan options.

Fragile-X Syndrome is a genetic disease caused by a mutation on the X chromosome. According to the National Institute of Health (NIH) and the National Center for Biotechnology Information (NCBI), it is the most common form of inherited intellectual and developmental disease. Following the recommendation of The American Congress of Obstetricians and Gynecologists (ACOG), Fragile-X Syndrome testing should be included in any carrier test if it is specifically requested for by the female patient.

A genetic mutation, also known as a genetic variant, is a change in the DNA. While most changes in our DNA are harmless, occasionally a DNA change can have serious consequences, including an increased risk for cancer or for a serious genetic disease. Several types of mutations are possible:

1. "Substitutions"

   1. "Missense Mutations" – a change in a single letter of DNA that leads to a change in the protein produced

   2. "Nonsense Mutations" – a single mutation that causes the code to stop the production of the protein chain earlier than it is supposed to

2. "Frameshift Mutations"

   1. "Insertions" – a letter of DNA inserted inappropriately into the DNA code. DNA “words” are all 3 letters long, so adding a letter results in many words shifting; hence the name “frameshift mutation”.

   2. "Deletions" – a letter of DNA inappropriately removed from the DNA code. DNA “words” are all 3 letters long, so removing a letter results in many words shifting; hence the name “frameshift mutation”.

3. "Rearrangements"

   1. Sections of DNA can become mixed up, disrupting certain proteins and their functions