Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle D A, Smith S, Uziel T, Sfez S, Ashkenazi M, Pecker I, Frydman M, Harnik R, Patanjali S R, Simmons A, Clines G A, Sartiel A, Gatti R A, Chessa L, Sanal O, Lavin M F, Jaspers N G, Taylor A M, Arlett C F, Miki T, Weissman S M, Lovett M, Collins F S, Shiloh Y
Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Israel.
Science. 1995 Jun 23;268(5218):1749-53. doi: 10.1126/science.7792600.
A gene, ATM, that is mutated in the autosomal recessive disorder ataxia telangiectasia (AT) was identified by positional cloning on chromosome 11q22-23. AT is characterized by cerebellar degeneration, immunodeficiency, chromosomal instability, cancer predisposition, radiation sensitivity, and cell cycle abnormalities. The disease is genetically heterogeneous, with four complementation groups that have been suspected to represent different genes. ATM, which has a transcript of 12 kilobases, was found to be mutated in AT patients from all complementation groups, indicating that it is probably the sole gene responsible for this disorder. A partial ATM complementary DNA clone of 5.9 kilobases encoded a putative protein that is similar to several yeast and mammalian phosphatidylinositol-3' kinases that are involved in mitogenic signal transduction, meiotic recombination, and cell cycle control. The discovery of ATM should enhance understanding of AT and related syndromes and may allow the identification of AT heterozygotes, who are at increased risk of cancer.
通过在11号染色体q22 - 23区域进行定位克隆，发现了一个在常染色体隐性疾病共济失调毛细血管扩张症（AT）中发生突变的基因ATM。AT的特征包括小脑退化、免疫缺陷、染色体不稳定、癌症易感性、辐射敏感性以及细胞周期异常。该疾病在遗传上具有异质性，有四个互补组，曾被怀疑代表不同的基因。ATM的转录本有12千碱基，在所有互补组的AT患者中均发现其发生了突变，这表明它可能是导致该疾病的唯一基因。一个5.9千碱基的部分ATM互补DNA克隆编码了一种推定蛋白，该蛋白与几种参与有丝分裂信号转导、减数分裂重组及细胞周期调控的酵母和哺乳动物磷脂酰肌醇-3'激酶相似。ATM的发现应能增进对AT及相关综合征的理解，并可能有助于识别患癌风险增加的AT杂合子。
