College of Osteopathic Medicine Faculty Articles

Title

Genetic Instability and Hematologic Disease Risk in Werner Syndrome Patients and Heterozygotes

ISBN or ISSN

0008-5472

Publication Title

Cancer Research

Volume

60

Issue

9

Publication Date / Copyright Date

5-1-2000

Abstract

Werner syndrome (WRN) is an uncommon autosomal recessive disease in which progeroid features are associated with genetic instability and an elevated risk of neoplasia. We have used the glycophorin A (GPA) somatic cell mutation assay to analyze genetic instability in vivo in WRN patients and heterozygotes. GPA variant frequencies were determined for 11 WRN patients and for 10 heterozygous family members who collectively carry 10 different WRN mutations. Genetic instability as measured by GPA Ø/N allele loss variant frequency was significantly increased, and this increase was strongly age-dependent in WRN patients. GPA Ø/N allele loss variants were also significantly elevated in heterozygous family members, thus providing the first evidence for in vivo genetic instability in heterozygous carriers in an autosomal recessive genetic instability syndrome. Our results and comparable data on other human genetic instability syndromes allow an estimate of the level of genetic instability that increases the risk of human bone marrow dysfunction or neoplasia.

Disciplines

Medical Specialties | Medicine and Health Sciences | Osteopathic Medicine and Osteopathy

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