A Japanese trichothiodystrophy patient with XPD mutations

Abstract

Trichothiodystrophy (TTD) is a rare autosomal recessive disorder characterized by sulfur-deficient brittle hair complicated with ichthyosis, physical and mental retardation, and proneness to infections. Approximately half of TTD patients exhibit cutaneous photosensitivity because of the defect of nucleotide excision repair. Three genes, XPB, XPD and TTDA, have been identified as causative genes of photosensitive TTD. These three genes are components of basal transcription factor IIH. Most TTD cases have been reported in Europe and North America. We report a severely affected Japanese TTD patient with XPD mutations. Interestingly, his father has ichthyotic skin. The alteration in the paternal allele was a nucleotide substitution leading to Arg-722 to Trp (R722W), as previously reported in TTD patients. The other alteration in the maternal allele was a novel 3-bp deletion at nucleotides 67-69, resulting in the deletion of Ser-23, which is located upstream of helicase motif I and is the closest to the N-terminal end of XPD in reported mutations. The expression study showed that the two alterations were causative mutations for TTD. In Asia, it is likely that there are TTD patients who have not been diagnosed. © 2011 The Japan Society of Human Genetics All rights reserved.