title: ATM mutations, haplotype analysis, and immunological status of Russian patients with ataxia telangiectasia.
abstract: Mutations in the ATM gene are responsible for the autosomal recessive disorder, ataxia telangiectasia (A-T). Mutations in different ethnic groups are distributed along the entire length of the large, 66 exon ATM gene. In this study, A-T patients from 16 Russian families were assessed for immunological status and ATM haplotype analysis, and screened for ATM mutations. Haplotype analysis was performed to enhance the efficiency of mutation detection. Mutations predicted to cause disease were identified in 19 of 32 alleles (59%), including a truncating mutation (c.5932G>T) that was identified in 8/32 (25%) alleles both by haplotype analysis and mutation screening. This mutation has been found in low abundance in other European A-T cohorts suggesting that this founder-effect mutation may be of Russian origin. The abundance of this mutation may allow for large-scale screening of cancer patients to help clarify the role of ATM in breast and other cancers. Nine of the remaining mutations were previously unreported, and add to the multitude of unique mutations found throughout the gene.
authors.affiliation: Department of Cancer and Cell Biology, Queensland Institute of Medical Research, 300 Herston Rd, Brisbane, 4029, Australia. geoffB@qimr.edu.au
authors.forename: Geoff W
authors.initials: GW
authors.lastname: Birrell
authors.forename: Katherine
authors.initials: K
authors.lastname: Kneebone
authors.forename: Michael
authors.initials: M
authors.lastname: Nefedov
authors.forename: Elena
authors.initials: E
authors.lastname: Nefedova
authors.forename: M N
authors.initials: MN
authors.lastname: Jartsev
authors.forename: Midori
authors.initials: M
authors.lastname: Mitsui
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gatti
authors.forename: Martin F
authors.initials: MF
authors.lastname: Lavin
mesh_terms: D000293:Adolescent; D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000276:immunology*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007223:Infant; D009154:Mutation / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012426:Russia; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases