Mutator phenotype of Werner syndrome is characterized by extensive deletions.

摘要: Werner syndrome (WS) is a rare autosomal-recessive disorder characterized by the premature appearance of features normal aging in young adults. The extensive phenotypic overlap between WS and suggests they may also share pathogenetic mechanisms. We reported previously that somatic cells from patients demonstrate propensity to develop chromosomal aberrations, including translocations, inversions, deletions, cell lines high spontaneous mutation rate 6-thioguanine resistance. report here biochemical molecular characterization mutations at X chromosome-linked hypoxanthine phosphoribosyltransferase (HPRT) locus 6-thioguanine-resistant control cells. Blot hybridization analysis 89 independent HPRT mutants lacking activity revealed an unusually proportion deletions as compared with (76% vs. 39%). Approximately half (58%) consisted loss greater than 20 kilobases DNA gene. These results suggest elevated rate, particularly play pathogenetically important roles several associated age-dependent human disease processes.