Identification of C7orf11 (TTDN1) gene mutations and genetic heterogeneity in nonphotosensitive trichothiodystrophy

7 páginas, 2 figuras, 1 tabla.
We have identified C7orf11, which localizes to the nucleus and is expressed in fetal hair follicles, as the first disease gene for nonphotosensitive trichothiodystrophy (TTD). C7orf11 maps to chromosome 7p14, and the disease locus has been designated “TTDN1” (TTDnonphotosensitive 1). Mutations were found in patients with Amish brittle-hair syndrome and in other nonphotosensititive TTD cases with mental retardation and decreased fertility but not in patients with Sabinas syndrome or Pollitt syndrome. Therefore, genetic heterogeneity in nonphotosensitive TTD is a feature similar to that observed in photosensitive TTD, which is caused by mutations in transcription factor II H (TFIIH) subunit genes. Comparative immunofluorescence analysis, however, suggests that C7orf11 does not influence TFIIH directly. Given the absence of cutaneous photosensitivity in the patients with C7orf11 mutations, together with the protein’s nuclear localization, C7orf11 may be involved in transcription but not DNA repair.
We acknowledge The Centre for Applied Genomics, the Genome Canada/Ontario Genome Institute, the Hospital for Sick Children Foundation, the Association Française contre les Myopathies, and the Dykstra Foundation in Detroit (grant to C.E.J.). S.W.S. is an Investigator of the Canadian Institutes of Health Research, a Scholar of the McLaughlin Centre for Molecular Medicine, and an International Scholar of the Howard Hughes Medical Institute.