A SINGLE ATAXIA-TELANGIECTASIA GENE WITH A PRODUCT SIMILAR TO PI-3 KINASE

A gene, ATM, that is mutated in the autosomal recessive disorder ataxi a telangiectasia (AT) was identified by positional cloning on chromoso me 11q22-23. AT is characterized by cerebellar degeneration, immunodef iciency, chromosomal instability, cancer predisposition, radiation sen sitivity, and cell cycle abnormalities. The disease is genetically het erogeneous, with four complementation groups that have been suspected to represent different genes. ATM, which has a transcript of 12 kiloba ses, was found to be mutated in AT patients from all complementation g roups, indicating that it is probably the sole gene responsible for th is disorder. A partial ATM complementary DNA clone of 5.9 kilobases en coded a putative protein that is similar to several yeast and mammalia n phosphatidylinositol-3' kinases that are involved in mitogenic signa l transduction, meiotic recombination, and cell cycle control. The dis covery of ATM should enhance understanding of AT and related syndromes and may allow the identification of AT heterozygotes, who are at incr eased risk of cancer.