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Comprehensive scanning of the ATM gene with DOVAM‐S
Author(s) -
Buzin Carolyn H.,
Gatti Richard A.,
Nguyen Vu Q.,
Wen Cindy Y.,
Mitui Midori,
Sanal Ozden,
Chen Jie Sheng,
Nozari Guity,
Mengos April,
Li Xuemin,
Fujimura Frank,
Sommer Steve S.
Publication year - 2003
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.10158
Subject(s) - frameshift mutation , missense mutation , genetics , biology , nonsense mutation , exon , single strand conformation polymorphism , gene , locus (genetics) , mutation , coding region , allele , microbiology and biotechnology
Mutation detection at the ATM locus has been difficult because of the large size of the gene (66 exons), the fact that mutations are located throughout the entire gene with no hotspots, and the difficulty of distinguishing mutations from polymorphisms. In this study, the entire coding region (exons 4–65) was scanned, as well as the adjacent intronic regions, using DOVAM‐S (Detection Of Virtually All Mutations‐SSCP), a robotically‐enhanced, multiplexed scanning method that is a highly sensitive modification of SSCP. Forty‐three unrelated patients and four obligate carriers were studied. Of the 90 expected mutant alleles, 71 were identified (79%). The mutations included 17 nonsense (24%), 20 frameshift (28%), 20 splice (28%), 10 missense (14%), one in‐frame deletion (1%), and three that alter the initiation codon (4%). Among the ataxia‐telangiectasia patients, two potentially causative mutations were identified in 30 individuals: 22 had two truncating mutations, four had one truncating and one missense mutation, three had two missense mutations, and one had a truncating mutation and an in‐frame deletion of three amino acids. For seven A‐T patients and all four obligate carriers, only one truncating mutation was detected. Six of the 43 A‐T patients had no detected mutations (14%). Twelve novel mutations and six novel polymorphisms were detected. The results of this complete scan of the ATM coding region showed that 86% of causative ATM mutations were truncating and 14% were missense. DOVAM‐S is a rapid, efficient method of performing A‐T diagnosis and carrier testing on a clinical time scale. Hum Mutat 21:123–131, 2003. © 2003 Wiley‐Liss, Inc.