Title

Analysis of genomic instability using multiple assays in a patient with Rothmund-Thomson syndrome

ISBN or ISSN

1399-0004

Publication Title

Clinical genetics

Volume

58

Issue

3

Publication Date / Copyright Date

9-1-2000

First Page

209

Last Page

215

DOI Number

10.1034/j.1399-0004.2000.580308.x

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.

Disciplines

Medicine and Health Sciences | Pharmacy and Pharmaceutical Sciences

Keywords

Adult, Blood Group Antigens, Child, Child, Preschool, Chromosome Fragility, DNA Damage, DNA Repair, Epoxy Compounds, Erythrocytes, Female, Flow Cytometry, Glycophorin, Humans, Infant, Infant, Newborn, Karyotyping, Loss of Heterozygosity, Lymphocytes, Male, Mitomycin, Mutation, Rothmund-Thomson Syndrome