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 O/N allele loss variant frequency was significantly increased, and this increase was strongly age-dependent in WRN patients. GPA O/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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Moser MJ,Bigbee WL,Grant SG,Emond MJ,Langlois RG,Jensen RH,Oshima J,Monnat RJ Jrsubject
Has Abstractpub_date
2000-05-01 00:00:00pages
2492-6issue
9eissn
0008-5472issn
1538-7445journal_volume
60pub_type
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