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

We report on a patient with Rothmund-Thomson syndrome (RTS) whose cytogenet ic evaluation showed a normal karyotype with no evidence of trisomy mosaici sm or chromosomal rearrangements. Cultured lymphocytes from the patient, he r mother, and a control exposed to mitomycin C and diepoxybutane did not sh ow increased sensitivity to the dialkylating agents. Unlike some previous r eports, we found no evidence of a deficiency in nucleotide excision repair, as measured with the functional unscheduled DNA synthesis assay. Glycophor in 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 R ecQ-related human diseases, and evidence for clonal expansion of a mutant c lone in the mother. Discrepant results in the literature may reflect true h eterogeneity in the disease or the fact that a consistent set of tests has not been applied to RTS patients.