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

Journal Article · Thu Feb 01 04:00:00 EST 1996 · American Journal of Human Genetics

OSTI ID:219856

Takayama, K; Salazar, E P; Thompson, L H ^[1]

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1. Lawrence Livermore National Lab., CA (United States); and others

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 (TTD1VI, 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. 39 refs., 2 figs., 3 tabs.

• DOE Contract Number: W-7405-ENG-48
• OSTI ID: 219856
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 2 Vol. 58; ISSN 0002-9297; ISSN AJHGAG
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
AMINO ACIDS
ANIMAL CELLS
DNA REPAIR
DNA SEQUENCING
DNA-CLONING
GENE MUTATIONS
GENES
GENETIC RADIATION EFFECTS
HEREDITARY DISEASES
MENTAL DISORDERS
NUCLEOTIDES
PHOTOSENSITIVITY
POLYMERASE CHAIN REACTION
RECESSIVE MUTATIONS
SKELETAL DISEASES
SKIN DISEASES
TRANSCRIPTION
ULTRAVIOLET RADIATION