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

Clin Genet. 2000 Sep;58(3):209-15. doi: 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.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Blood Group Antigens / genetics
  • Child
  • Child, Preschool
  • Chromosome Fragility / genetics*
  • DNA Damage / drug effects
  • DNA Repair / genetics
  • Epoxy Compounds / pharmacology
  • Erythrocytes / metabolism
  • Erythrocytes / pathology
  • Female
  • Flow Cytometry
  • Glycophorins / genetics
  • Humans
  • Infant
  • Infant, Newborn
  • Karyotyping
  • Loss of Heterozygosity / genetics
  • Lymphocytes / cytology
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Lymphocytes / pathology
  • Male
  • Mitomycin / pharmacology
  • Mutation / genetics
  • Rothmund-Thomson Syndrome / blood
  • Rothmund-Thomson Syndrome / genetics*
  • Rothmund-Thomson Syndrome / pathology

Substances

  • Blood Group Antigens
  • Epoxy Compounds
  • Glycophorins
  • Mitomycin
  • diepoxybutane