ATM mutations in patients with ataxia telangiectasia screened by a hierarchical strategy

Tomonari Sasaki, Huaize Tian, Yoji Kukita, Masakazu Inazuka, Tomoko Tahira, Takashi Imai, Masatake Yamauchi, Toshiyuki Saito, Tada Aki Hori, Tomoko Hashimoto-Tamaoki, Kenshi Komatsu, Osamu Nikaido, Kenshi Hayashi

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17 Citations (Scopus)


ATM has been identified as a gene that is responsible for ataxia telangiectasia (AT), a pleiotropic disorder of autosomal recessive inheritance. While many mutations of this gene in AT patients of various ethnicities have been reported, data on Japanese patients are scarce. In this report, we present the results of a thorough survey of ATM mutations in 14 unrelated AT patients, with an emphasis on Japanese subjects. We used a hierarchical strategy in which we extensively analyzed the entire coding region of the cDNA. In the first stage, point mutations were sought by PCR- SSCP in short patches. In the second and third stages, the products of medium- and long-patch PCR, each covering the entire region, were examined by agarose gel electrophoresis to search for length changes. We found a total of 15 mutations (including 12 new) and 4 polymorphisms. Abnormal splicing of ATM was frequent among Japanese, and no hotspot was obvious, suggesting no strong founder effects in this ethnic group. Eleven patients carried either one homozygous or two compound heterozygous mutations, one patient carried only one detectable heterozygous mutation, and no mutation was found in two patients. Overall, mutations were found in at least 75% of the different ATM alleles examined. Possible reasons for the inability to detect mutations in some patients are discussed.

Original languageEnglish
Pages (from-to)186-195
Number of pages10
JournalHuman mutation
Issue number3
Publication statusPublished - 1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


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