Takayama K, Salazar E P, Broughton B C, Lehmann A R, Sarasin A, Thompson L H, Weber C A
Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, CA 94551, USA.
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.
毛发硫营养不良症（TTD）是一种罕见的常染色体隐性疾病，其特征为头发脆弱且含硫量降低、鱼鳞病、特殊面容以及智力和生长发育迟缓。约50%的TTD患者存在临床光敏性，但这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归因于与易患癌症的遗传性疾病着色性干皮病D组（XP-D）相同的基因位点缺陷。对来自三种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区域内以及先前确定的解旋酶功能域内存在突变。细胞株的各种临床表现和DNA修复特征可与在ERCC2基因位点发现的特定突变相关联。Arg658突变为His或Cys与具有中等紫外线敏感性的TTD细胞株相关，Arg722突变为Trp与高度紫外线敏感的TTD细胞株相关，Arg683突变为Trp与XP-D相关。在XP-D和TTD细胞株中均发现了Arg616突变为Pro的等位基因或Leu461突变为Val以及716 - 730缺失的联合突变。
