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, b oth in nucleotide excision repair of DNA damage and in basal transcrip tion. Mutations in the XPD gene can result in three distinct clinical phenotypes, XP, trichothiodystrophy (TTD), and XP with Cockayne syndro me. To determine if the clinical phenotypes of XP and TTD can be attri buted 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 dif fered between XP and TTD, but there are three sites at which the same mutation is found in XP and TTD patients. Since the corresponding pati ents were all compound heterozygotes with different mutations in the t wo alleles, the alleles mere tested separately in a yeast complementat ion assay, The mutations which are found in both XP and TTD patients b ehaved as null alleles, suggesting that tile disease phenotype was det ermined by the other allele. If we eliminate the null mutations, the r emaining mutagenic pattern is consistent with the site of the mutation determining the phenotype.