Xeroderma Pigmentosum and Trichothiodystrophy are Associated with Different Mutations in the XPD (ERCC2) Repair/Transcription Gene

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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1997-08, Vol.94 (16), p.8658-8663
Main Authors: Taylor, Elaine M., Broughton, Bernard C., Botta, Elena, Stefanini, Miria, Sarasin, Alain, Nicolaas G. J. Jaspers, Fawcett, Heather, Harcourt, Susan A., Arlett, Colin F., Lehmann, Alan R.
Format: Article
Language:English
Subjects:
Alleles
Biological Sciences
Cell culture techniques
Cell fusion
Cell Line
Cell lines
DNA
DNA Helicases
DNA repair
DNA Repair - genetics
DNA Repair - radiation effects
DNA-Binding Proteins
Fibroblasts - radiation effects
Genetic mutation
Genetics
Hair Diseases - genetics
Humans
Mutation
Neurons
Phenotypes
Proteins - genetics
Transcription Factors
Ultraviolet Rays
Viability
Xeroderma Pigmentosum - genetics
Xeroderma Pigmentosum Group D Protein
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.94.16.8658