title: Analysis of microsatellite instability and hypermutation of immunoglobulin variable genes in Werner syndrome.
abstract: Werner syndrome (WS) is a human premature aging syndrome, which is associated with high frequencies of neoplasia and genetic instability. We have examined the occurrence of microsatellite instability, which may result from defective mismatch repair, in lymphoblastoid cell lines derived from nine WS patients. Instability was measured at the D2S123 locus by gel analysis of PCR products. Three WS cell lines had 4-13% altered alleles, compared with 0% in the other six lines. The increased frequency of microsatellite instability could not readily be associated with overt cancer or any other known clinical condition in the three patients. To examine whether the WS defect affected the humoral immune system, we measured the hypermutation of immunoglobulin variable genes in peripheral blood cells from the WS patient who donated the cell line with the highest frequency of microsatellite instability. The frequency and pattern of mutation was similar to that from normal individuals, suggesting that the Werner protein is not involved in generating hypermutation.
authors.affiliation: Laboratory of Molecular Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: K
authors.initials: K
authors.lastname: Rosner
authors.forename: D B
authors.initials: DB
authors.lastname: Winter
authors.forename: G L
authors.initials: GL
authors.lastname: Skovgaard
authors.forename: J
authors.initials: J
authors.lastname: Oshima
authors.forename: P J
authors.initials: PJ
authors.lastname: Gearhart
authors.forename: V A
authors.initials: VA
authors.lastname: Bohr
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D022801:Complementarity Determining Regions; D018076:DNA, Complementary; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009154:Mutation; D014898:Werner Syndrome / Q000235:genetics* / Q000276:immunology
chemical_list: D022801:Complementarity Determining Regions; D018076:DNA, Complementary; D007135:Immunoglobulin Variable Region