title: Identical mutations in the CSB gene associated with either Cockayne syndrome or the DeSanctis-cacchione variant of xeroderma pigmentosum.
abstract: Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are two hereditary disorders 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 clinical manifestations strongly reminiscent of a severe form of XP were unexpectedly 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 showed that these patients had identical alterations to those in a patient with the clinical features of the classical form of CS. These data, together with 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 inactivating mutation underlies different pathological phenotypes indicates that there is no simple correlation between the molecular defect and the clinical features. Therefore, alterations in the CSB gene give rise to the same repair defect at the cellular level but other genetic and/or environmental factors determine the pathological phenotype.
authors.affiliation: Istituto di Genetica Biochimica ed Evoluzionistica CNR, Via Abbiategrasso, 207-27100 Pavia, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Colella
authors.forename: T
authors.initials: T
authors.lastname: Nardo
authors.forename: E
authors.initials: E
authors.lastname: Botta
authors.forename: A R
authors.initials: AR
authors.lastname: Lehmann
authors.forename: M
authors.initials: M
authors.lastname: Stefanini
mesh_terms: D002478:Cells, Cultured; D003057:Cockayne Syndrome / Q000235:genetics*; D018388:Codon, Terminator; D004265:DNA Helicases / Q000235:genetics*; D045643:DNA Repair Enzymes; D014644:Genetic Variation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D020125:Mutation, Missense; D009679:Nuclear Family; D017354:Point Mutation; D000075223:Poly-ADP-Ribose Binding Proteins; D014983:Xeroderma Pigmentosum / Q000235:genetics*
chemical_list: D018388:Codon, Terminator; D000075223:Poly-ADP-Ribose Binding Proteins; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes