title: Xeroderma pigmentosum and trichothiodystrophy are associated with different mutations in the XPD (ERCC2) repair/transcription gene.
abstract: The xeroderma pigmentosum group D (XPD) protein has a dual function, both in nucleotide excision repair of DNA damage and in basal transcription. Mutations in the XPD gene can result in three distinct clinical phenotypes, XP, trichothiodystrophy (TTD), and XP with Cockayne syndrome. To determine if the clinical phenotypes of XP and TTD can be attributed to the sites of the mutations, we have identified the mutations in a large group of TTD and XP-D patients. Most sites of mutations differed between XP and TTD, but there are three sites at which the same mutation is found in XP and TTD patients. Since the corresponding patients were all compound heterozygotes with different mutations in the two alleles, the alleles were tested separately in a yeast complementation assay. The mutations which are found in both XP and TTD patients behaved as null alleles, suggesting that the disease phenotype was determined by the other allele. If we eliminate the null mutations, the remaining mutagenic pattern is consistent with the site of the mutation determining the phenotype.
authors.affiliation: Medical Research Council Cell Mutation Unit, Sussex University, Falmer, Brighton BN1 9RR, United Kingdom.
authors.forename: E M
authors.initials: EM
authors.lastname: Taylor
authors.forename: B C
authors.initials: BC
authors.lastname: Broughton
authors.forename: E
authors.initials: E
authors.lastname: Botta
authors.forename: M
authors.initials: M
authors.lastname: Stefanini
authors.forename: A
authors.initials: A
authors.lastname: Sarasin
authors.forename: N G
authors.initials: NG
authors.lastname: Jaspers
authors.forename: H
authors.initials: H
authors.lastname: Fawcett
authors.forename: S A
authors.initials: SA
authors.lastname: Harcourt
authors.forename: C F
authors.initials: CF
authors.lastname: Arlett
authors.forename: A R
authors.initials: AR
authors.lastname: Lehmann
mesh_terms: D002460:Cell Line; D004265:DNA Helicases; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects; D004268:DNA-Binding Proteins; D005347:Fibroblasts / Q000528:radiation effects; D006201:Hair Diseases / Q000235:genetics*; D006801:Humans; D009154:Mutation; D011506:Proteins / Q000235:genetics*; D014157:Transcription Factors; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics*; D051759:Xeroderma Pigmentosum Group D Protein
chemical_list: D004268:DNA-Binding Proteins; D011506:Proteins; D014157:Transcription Factors; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human