Defects in the DNA repair and transcription gene ERCC2(XPD) in trichothiodystrophy

Am J Hum Genet. 1996 Feb;58(2):263-70.


Trichothiodystrophy (TTD) is a rare autosomal recessive disorder characterized by brittle hair with reduced sulfur content, ichthyosis, peculiar face, and mental and growth retardation. Clinical photosensitivity is present in approximately 50% of TTD patients but is not associated with an elevated frequency of cancers. Previous complementation studies show that the photosensitivity in nearly all of the studied patients is due to a defect in the same genetic locus that underlies the cancer-prone genetic disorder xeroderma pigmentosum group D (XP-D). Nucleotide-sequence analysis of the ERCC2 cDNA from three TTD cell strains (TTD1V1, TTD3VI, and TTD1RO) revealed mutations within the region from amino acid 713-730 and within previously identified helicase functional domains. The various clinical presentations and DNA repair characteristics of the cell strains can be correlated with the particular mutations found in the ERCC2 locus. Mutations of Arg658 to either His or Cys correlate with TTD cell strains with intermediate UV-sensitivity, mutation of Arg722 to Trp correlates with highly UV-sensitive TTD cell strains, and mutation of Arg683 to Trp correlates with XP-D. Alleles with mutation of Arg616 to Pro or with the combined mutation of Leu461 to Val and deletion of 716-730 are found in both XP-D and TTD cell strains.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Base Sequence
  • Cell Survival
  • Cells, Cultured
  • Cloning, Molecular
  • DNA Helicases*
  • DNA Repair / genetics*
  • DNA-Binding Proteins*
  • Female
  • Hair / metabolism
  • Hair Diseases / genetics*
  • Humans
  • Infant
  • Male
  • Molecular Sequence Data
  • Photosensitivity Disorders / genetics
  • Photosensitivity Disorders / physiopathology
  • Point Mutation / genetics
  • Proteins / chemistry
  • Proteins / genetics*
  • Sequence Alignment
  • Sequence Analysis
  • Sequence Deletion / genetics
  • Transcription Factors*
  • Ultraviolet Rays / adverse effects
  • Xeroderma Pigmentosum / genetics
  • Xeroderma Pigmentosum Group D Protein


  • DNA-Binding Proteins
  • Proteins
  • Transcription Factors
  • DNA Helicases
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human

Associated data

  • GENBANK/U04967
  • GENBANK/U04968