Two individuals with features of both xeroderma pigmentosum and trichothiodystrophy highlight the complexity of the clinical outcomes of mutations in the XPD gene
Two individuals with features of both xeroderma pigmentosum and trichothiodystrophy highlight the complexity of the clinical outcomes of mutations in the XPD gene
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DOI：
10.1093/hmg/10.22.2539
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发表时间：
2001-10-15
影响因子：
3.5
通讯作者：
Lehmann, AR
中科院分区：
文献类型：
--
作者：
Broughton, BC;Berneburg, M;Lehmann, AR
着色性干皮病 D 组 (XPD) 蛋白是具有 DNA 解旋酶活性的转录因子 TFIIH 的亚基。 TFIIH 有两个功能，基础转录和核苷酸切除修复。 XPD 突变影响 DNA 修复但不影响转录，导致皮肤癌易发疾病——着色性干皮病 (XP)。如果转录也受到影响，则结果是多系统疾病毛发硫营养不良 (TTD)，其中没有皮肤癌倾向，或者在极少数情况下，XP 合并科凯恩综合征。迄今为止，尚未见 XP 和 TTD 联合临床特征的报道。我们现在已经确定两名患者具有这两种疾病的某些特征。其中，XP189MA 是一名 3 岁女孩，患有阳光敏感症、精神和身体发育迟缓，她具有以前未报道过的 XPD 突变，并且几乎检测不到核苷酸切除修复的水平。另一位是 XP38BR，是一名 28 岁女性，患有日光敏感、色素沉着变化和 XP 典型的皮肤癌，她具有先前已发现的突变，但仅限于没有 XP 特征的 TTD 患者。 XP38BR的紫外线损伤修复水平显着高于其他具有相同突变的患者。对于这两名患者，偏光显微镜显示头发呈“虎尾”外观，发干的氨基酸分析显示含硫蛋白质的水平介于正常人和 TTD 个体之间。我们的研究结果强调了 XPD 基因中基因型与表型关系的复杂性。
The xeroderma pigmentosum group D (XPD) protein is a subunit of transcription factor TFIIH with DNA helicase activity. TFIIH has two functions, in basal transcription and nucleotide excision repair. Mutations in XPD that affect DNA repair but not transcription result in the skin cancer-prone disorder, xeroderma pigmentosum (XP). If transcription is also affected, the result is the multi-system disorder trichothiodystrophy (TTD), in which there is no skin cancer predisposition, or in rare cases, XP combined with Cockayne syndrome. Up till now there have been no reports of combined clinical features of XP and TTD. We have now identified two patients with some features of both these disorders. One of these, XP189MA, a 3-year-old girl with sun sensitivity, mental and physical developmental delay, has XPD mutations not previously reported, and barely detectable levels of nucleotide excision repair. The other, XP38BR, a 28-year-old woman with sun sensitivity, pigmentation changes and skin cancers typical of XP, has a mutation that has been identified previously, but only in TTD patients with no features of XP. The level of repair of UV damage in XP38BR is substantially higher than that in other patients with the same mutation. With both patients, polarized light microscopy revealed a 'tiger-tail' appearance of the hair, and amino acid analysis of the hairshafts show levels of sulfur-containing proteins intermediate between those of normal and TTD individuals. Our findings highlight the complexities of genotype-phenotype relationships in the XPD gene.