Ataxia Telangiectasia - Genetics and Information About A-T Carriers

Genetics and Information About A-T Carriers

A-T is caused by mutations in the ATM (Ataxia Telangiectasia Mutated) gene which was cloned in 1995. ATM is located on human chromosome 11 (11q22.3) and is made up of 66 exons spread across 150kb of genomic DNA.

The mode of inheritance for A-T is autosomal recessive. Each parent is a carrier, meaning that they have one normal copy of the A-T gene (ATM) and one copy which is mutated. A-T occurs if a child inherits the mutated A-T gene from each parent, so in a family with two carrier parents, there is 1 chance in 4 that a child born to the parents will have the disorder. Prenatal diagnosis (and carrier detection) can be carried out in families if the errors (mutation) in an affected child’s two ATM genes have been identified. The process of getting this done can be complicated and as it requires time should be arranged before conception.

Looking for mutations in the ATM gene of an unrelated person (for example, the spouse of a known A-T carrier) presents significant challenges. Genes often have variant spellings (polymorphisms) which do not affect function. In a gene as large as ATM, such variant spellings are likely to occur and doctors cannot always predict if a specific variant will or will not cause disease. Genetic counseling can help family members of an A-T patient understand what can or cannot be tested, and how the test results should be interpreted.

Carriers of A-T, such as the parents of a person with A-T, have one mutated copy of the ATM gene and one normal copy. They are generally healthy, but there is an increased risk of breast cancer in women. This finding has been confirmed in a variety of different ways, and is the subject of current research. Standard surveillance (including monthly breast self-exams and mammography at the usual schedule for age) is recommended, unless additional tests are indicated because the individual has other risk factors (e.g., family history of breast cancer).