DNA-REPAIR CHARACTERISTICS AND MUTATIONS IN THE ERCC2 DNA-REPAIR AND TRANSCRIPTION GENE IN A TRICHOTHIODYSTROPHY PATIENT

Patient TTD183ME is male and has typical trichothiodystrophy character istics, including brittle hair, ichthyosis, characteristic face with r eceding chin and protruding ears, sun sensitivity, and mental and grow th retardation, The relative amount of NER carried out by a TTD183ME f ibroblast cell strain after ultraviolet (UV) exposure was similar to 6 5% of normal as determined by a method that converts repair patches in to quantifiable DNA breaks. UV survival curves show a reduction in sur vival only at doses greater than 4 J/m(2), Nucleotide sequence analysi s of the ERCC2 (XPD) DNA repair and transcription gene cDNA revealed b oth a Leu461-to-Val substitution and a deletion of amino acids 716-730 in one allele and an Ala725-to-Pro substitution in the other allele. The first allele has also been reported in one xeroderma pigmentosum g roup D patient and two other trichothiodystrophy patients, while the s econd allele has not been previously reported. Comparisons suggest tha t the mutation of Ala725 to Pro correlates with TTD with intermediate UV sensitivity. (C) 1997 Wiley-Liss, Inc.