title: Analysis of genomic instability using multiple assays in a patient with Rothmund-Thomson syndrome.
abstract: We report on a patient with Rothmund-Thomson syndrome (RTS) whose cytogenetic evaluation showed a normal karyotype with no evidence of trisomy mosaicism or chromosomal rearrangements. Cultured lymphocytes from the patient, her mother, and a control exposed to mitomycin C and diepoxybutane did not show increased sensitivity to the dialkylating agents. Unlike some previous reports, we found no evidence of a deficiency in nucleotide excision repair, as measured with the functional unscheduled DNA synthesis assay. Glycophorin A analysis of red blood cells for somatic mutation revealed suspiciously high frequencies of both allele loss and loss-and-duplication variants in the blood of the patient, a pattern consistent with observations in other RecQ-related human diseases, and evidence for clonal expansion of a mutant clone in the mother. Discrepant results in the literature may reflect true heterogeneity in the disease or the fact that a consistent set of tests has not been applied to RTS patients.
authors.affiliation: Department of Environmental and Occupational Health, University of Pittsburgh, PA, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Grant
authors.forename: S L
authors.initials: SL
authors.lastname: Wenger
authors.forename: J J
authors.initials: JJ
authors.lastname: Latimer
authors.forename: D
authors.initials: D
authors.lastname: Thull
authors.forename: L W
authors.initials: LW
authors.lastname: Burke
mesh_terms: D000328:Adult; D001789:Blood Group Antigens / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002873:Chromosome Fragility / Q000235:genetics*; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000235:genetics; D004852:Epoxy Compounds / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006021:Glycophorins / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D019656:Loss of Heterozygosity / Q000235:genetics; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D016685:Mitomycin / Q000494:pharmacology; D009154:Mutation / Q000235:genetics; D011038:Rothmund-Thomson Syndrome / Q000097:blood / Q000235:genetics* / Q000473:pathology
chemical_list: D001789:Blood Group Antigens; D004852:Epoxy Compounds; D006021:Glycophorins; D016685:Mitomycin; C007366:diepoxybutane