A high frequency of distinct ATM gene mutations in ataxia-telangiectasia

摘要: The clinical features of the autosomal recessive disorder ataxia-telangiectasia (AT) include a progressive cerebellar ataxia, hypersensitivity to ionizing radiation, and an increased susceptibility malignancies. Epidemiological studies have suggested that AT heterozygotes may also be at risk for malignancy, possibly as consequence radiation exposure. A gene mutated in patients (ATM) has recently been isolated, making mutation screening both general population possible. Because relatively large size ATM gene, design programs will depend on types distribution mutations population. In this report, we describe 30 identified panel unrelated controls. Twenty-five were distinct, most compound heterozygotes. frequently detected was found three different families had previously reported five others. This corresponds frequency 8% all mutations. Twenty-two alterations observed would predicted lead protein truncation sites scattered throughout molecule. Two fibroblast cell lines, which displayed normal responses proved heterozygous ATM. These observations suggest carrier sufficiently high make practical. However, such need done prospectively, is, by searching new rather than just those already families.