MUTATIONS IN THE XERODERMA-PIGMENTOSUM GROUP-D DNA REPAIR TRANSCRIPTION GENE IN PATIENTS WITH TRICHOTHIODYSTROPHY/

DNA repair defects in the xeroderma pigmentosum (XP) group D complemen tation group can be associated with the clinical features of two quite different disorders; XP, a sun-sensitive and cancer-prone disorder, o r trichothiodystrophy (TTD) which is characterized by sulphur-deficien t brittle hair and a variety of other associated abnormalities, but no skin cancer. The XPD gene product, a DNA helicase, is required for nu cleotide excision repair and recent evidence has demonstrated a role i n transcription. We have now identified causative mutations in XPD in four TTD patients. The patients are all compound heterozygotes and the locations of the mutations enable us to suggest relationships between different domains in the gene and its roles in excision repair and tr anscription.