title: Detection of heterozygous carriers of the ataxia-telangiectasia (ATM) gene by G2 phase chromosomal radiosensitivity of peripheral blood lymphocytes.
abstract: In ataxia-telangiectasia (A-T) patients, mutations in a single gene, ATM, result in an autosomal recessive syndrome that embraces a variety of clinical features and manifests extreme radiosensitivity and a strong pre-disposition to malignancy. Heterozygotes for the ATM gene have no clinical expression of A-T but may be cancer prone with a moderate increase in in vitro radiosensitivity. We performed a blind chromosomal analysis on G2-phase lymphocytes from 7 unrelated A-T patients, 13 obligate A-T heterozygotes (parents of the patients), and 14 normal controls following X-irradiation with 1 Gy in order to evaluate this cytogenetic method as a tool for detection of ATM carriers. Both A-T homozygotes and heterozygotes showed significantly increased levels of radiation-induced chromatid damage relative to that of normal controls. These results show that the G2-phase chromosomal radiosensitivity assay can be used for the detection of A-T heterozygotes. In combination with molecular genetic analyses, this test may be of value in studies of familial and sporadic cancers aimed at determination of the potential involvement of ATM mutations in tumor risk or development.
authors.affiliation: Laboratoire de Cytogénétique Médicale, Faculté de Médecine, Clermont-Ferrand, France.
authors.forename: A
authors.initials: A
authors.lastname: Tchirkov
authors.forename: J O
authors.initials: JO
authors.lastname: Bay
authors.forename: D
authors.initials: D
authors.lastname: Pernin
authors.forename: Y J
authors.initials: YJ
authors.lastname: Bignon
authors.forename: P
authors.initials: P
authors.lastname: Rio
authors.forename: M
authors.initials: M
authors.lastname: Grancho
authors.forename: F
authors.initials: F
authors.lastname: Kwiatkowski
authors.forename: M
authors.initials: M
authors.lastname: Giollant
authors.forename: P
authors.initials: P
authors.lastname: Malet
authors.forename: P
authors.initials: P
authors.lastname: Verrelle
mesh_terms: D000293:Adolescent; D000328:Adult; D001260:Ataxia Telangiectasia / Q000235:genetics*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002842:Chromatids / Q000528:radiation effects; D002869:Chromosome Aberrations; D004268:DNA-Binding Proteins; D005260:Female; D016195:G2 Phase / Q000528:radiation effects; D006580:Genetic Carrier Screening / Q000379:methods*; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics*; D011836:Radiation Tolerance; D025521:Tumor Suppressor Proteins; D014965:X-Rays
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases