title: Trichothiodystrophy group A: a first Japanese patient with a novel homozygous nonsense mutation in the GTF2H5 gene.
abstract: Trichothiodystrophy group A (TTD-A) is one of the three types of photosensitive TTD and is a very rare genodermatosis with deficient post-ultraviolet (UV) DNA repair. We herein describe the first Japanese case with a novel mutation in the GTF2H5 gene responsible for TTD-A. A 5-year-old male, born as a collodion baby from healthy non-consanguineous parents, exhibited sun sensitivity, brittle hair, ichthyosis, cataracts and mental/physical retardation. He demonstrated neither neurological abnormalities nor pigmentary changes following sun exposure. The patient's primary fibroblasts were hypersensitive to killing by UV (D0  = 1.5 J/m(2) ), and the post-UV unscheduled DNA synthesis was 13% of normal. A host cell reactivation complementation analysis showed a decreased DNA capacity without recovery after transfecting any xeroderma pigmentosum genes. We identified a novel homozygous mutation (c.166G>T) in the coding region of the GTF2H5 gene that resulted in a predicted amino acid change: p.E55X. Thus far, only one Japanese case of TTD with a mutation of the XPD gene had been reported. The present case is the first of TTD-A and the second case of TTD in Japan, suggesting that it is necessary to differentiate TTD from other photosensitive disorders, although the incidence of TTD is very low in Japan compared to that observed in Western countries.
authors.affiliation: Department of Dermatology, Osaka Medical College, Osaka; Department of Photomedical Genomics, Basic Medical Photonics Laboratory, Medical Photonics Research Center, Hamamatsu University School of Medicine, Hamamatsu.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Moriwaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saruwatari
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Kanzaki
authors.forename: Takuro
authors.initials: T
authors.lastname: Kanekura
authors.forename: Shinsei
authors.initials: S
authors.lastname: Minoshima
mesh_terms: D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002675:Child, Preschool; D018389:Codon, Nonsense; D004247:DNA / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D005260:Female; D006720:Homozygote; D006801:Humans; D007564:Japan; D008297:Male; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics*; D054463:Trichothiodystrophy Syndromes / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; C512380:GTF2H5 protein, human; D014157:Transcription Factors; D004247:DNA
keywords: DNA repair; Japanese; brittle hair; photosensitivity; trichothiodystrophy group A