Defects in the DNA repair and transcription gene ERCC2(XPD) in trichothiodystrophy.
Defects in the DNA repair and transcription gene ERCC2(XPD) in trichothiodystrophy.
复制标题
DOI：
--
复制
发表时间：
1996-02
影响因子：
9.8
通讯作者：
K. Takayama;E. Salazar;B. Broughton;A. Lehmann;A. Sarasin;L. H. Thompson;C. Weber
中科院分区：
文献类型：
--
作者：
K. Takayama;E. Salazar;B. Broughton;A. Lehmann;A. Sarasin;L. H. Thompson;C. Weber
毛硫营养不良症（TTD）是一种罕见的常染色体隐性遗传病，其特征是头发易脆，硫含量降低，鱼鳞病，面容奇特，智力和生长迟缓。临床光敏性存在于约50%的TTD患者中，但与癌症发病率升高无关。先前的互补研究表明，几乎所有研究患者的光敏性都是由于同一基因位点的缺陷，该基因位点是易患癌症的遗传性疾病D组着色性干皮病（XP-D）的基础。对三株TTD细胞株（TTD1V1、TTD3VI和TTD1RO）的ERCC2 cDNA进行核苷酸序列分析，发现在氨基酸713-730区域和先前确定的解旋酶功能域内发生突变。这些细胞株的各种临床表现和DNA修复特征可能与ERCC2位点上发现的特定突变有关。Arg658突变为His或Cys与中等紫外线敏感性的TTD细胞株相关，Arg722突变为Trp与高紫外线敏感性的TTD细胞株相关，Arg683突变为Trp与XP-D相关。在XP-D和TTD细胞株中均发现Arg616向Pro突变或Leu461向Val联合突变和716-730缺失的等位基因。
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.