title: Heterozygote detection through bleomycin-induced G2 chromatid breakage in dyskeratosis congenita families.
abstract: We determined the mean number of chromatid breaks per cell (b/c) in the bleomycin-treated lymphocytes of 10 patients with dyskeratosis congenita (DC) and 26 of their relatives to ascertain whether bleomycin sensitivity would distinguish DC heterozygotes from normal individuals. We observed a significantly higher mean number of chromatid b/c in DC patients and obligate heterozygotes (patients versus controls, p less than 0.0001; heterozygotes versus controls, p = 0.0076, Mann-Whitney rank-sum test). Unequivocal heterozygote detection was not possible owing to overlap of the b/c values of patients, heterozygotes, and controls, but our findings provided strong evidence of a link between autosomal recessive as well as X-linked recessive DC mutations and bleomycin sensitivity in homozygous, hemizygous, and heterozygous individuals.
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston 29425.
authors.forename: Y
authors.initials: Y
authors.lastname: Ning
authors.forename: Y
authors.initials: Y
authors.lastname: Yongshan
authors.forename: G S
authors.initials: GS
authors.lastname: Pai
authors.forename: A J
authors.initials: AJ
authors.lastname: Gross
mesh_terms: D000293:Adolescent; D001761:Bleomycin / Q000494:pharmacology*; D002648:Child; D002842:Chromatids / Q000187:drug effects*; D005260:Female; D016195:G2 Phase / Q000187:drug effects*; D006580:Genetic Carrier Screening; D006801:Humans; D007972:Leukoplakia, Oral / Q000150:complications / Q000235:genetics*; D008214:Lymphocytes / Q000648:ultrastructure; D008297:Male; D009262:Nails / Q000473:pathology*; D010375:Pedigree; D010859:Pigmentation Disorders / Q000150:complications / Q000235:genetics; D012871:Skin Diseases / Q000150:complications / Q000235:genetics; D013577:Syndrome
chemical_list: D001761:Bleomycin