Identical mutations in the CSB gene associated with either Cockayne syndrome or the DeSanctis-Cacchione variant of xeroderma pigmentosum

Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are two hereditary di sorders in which photosensitivity is associated with distinct clinical and cellular phenotypes and results from genetically different defects. We have identified the primary molecular alteration in two patients in whom clinic al manifestations strongly reminiscent of a severe form of XP were unexpect edly associated with the CS cellular phenotype and with a defect in the CSB gene. Sequencing of the CSB-coding region in both cDNA and genomic DNA sho wed that these patients had identical alterations to those in a patient wit h the clinical features of the classical form of CS. These data, together w ith fluorescence in situ hybridization analysis, demonstrated that the two siblings with XP as well as the CS patient were homozygous for the same CSB mutated allele, containing a silent C2830T change and a nonsense mutation C2282T converting Arg735 to a stop codon. The finding that the same inactiv ating mutation underlies different pathological phenotypes indicates that t here is no simple correlation between the molecular defect and the clinical features. Therefore, alterations in the CSB gene give rise to the same rep air defect at the cellular level but other genetic and/or environmental fac tors determine the pathological phenotype.