title: Identification of C7orf11 (TTDN1) gene mutations and genetic heterogeneity in nonphotosensitive trichothiodystrophy.
abstract: 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" (TTD nonphotosensitive 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.
authors.affiliation: Program in Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakabayashi
authors.forename: Daniela
authors.initials: D
authors.lastname: Amann
authors.forename: Yan
authors.initials: Y
authors.lastname: Ren
authors.forename: Ulpu
authors.initials: U
authors.lastname: Saarialho-Kere
authors.forename: Nili
authors.initials: N
authors.lastname: Avidan
authors.forename: Simone
authors.initials: S
authors.lastname: Gentles
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: MacDonald
authors.forename: Erik G
authors.initials: EG
authors.lastname: Puffenberger
authors.forename: Angela M
authors.initials: AM
authors.lastname: Christiano
authors.forename: Amalia
authors.initials: A
authors.lastname: Martinez-Mir
authors.forename: Julio C
authors.initials: JC
authors.lastname: Salas-Alanis
authors.forename: Renata
authors.initials: R
authors.lastname: Rizzo
authors.forename: Esther
authors.initials: E
authors.lastname: Vamos
authors.forename: Anja
authors.initials: A
authors.lastname: Raams
authors.forename: Clifford
authors.initials: C
authors.lastname: Les
authors.forename: Eric
authors.initials: E
authors.lastname: Seboun
authors.forename: Nicolaas G J
authors.initials: NG
authors.lastname: Jaspers
authors.forename: Jacques S
authors.initials: JS
authors.lastname: Beckmann
authors.forename: Charles E
authors.initials: CE
authors.lastname: Jackson
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D004476:Ectodermal Dysplasia / Q000235:genetics*; D005260:Female; D006197:Hair / Q000002:abnormalities*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016366:Open Reading Frames; D010375:Pedigree; D010787:Photosensitivity Disorders / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013577:Syndrome
chemical_list: D004247:DNA