Chen E, Cleaver J E, Weber C A, Packman S, Barkovich A J, Koch T K, Williams M L, Golabi M, Price V H
Department of Pediatrics (Division of Genetics), University of California, San Francisco 94143.
J Invest Dermatol. 1994 Nov;103(5 Suppl):154S-158S. doi: 10.1111/1523-1747.ep12399493.
Trichothiodystrophy (TTD), an autosomal recessive disorder characterized by sulfur-deficient brittle hair, identifies a group of genetic disorders with an altered synthesis of high-sulfur matrix proteins and a defect in excision repair of ultraviolet damage in fibroblasts of most TTD patients. In contrast to patients with xeroderma pigmentosum (XP), TTD patients do not have an increased frequency of skin cancers. TTD patients may be grouped into four categories: 1) those without photosensitivity and without a defect in excision repair of UV damage; 2) those without photosensitivity and with an excision-repair defect in the same gene as in XP-D (complementation group D); 3) those with photosensitivity and with the XP-D repair defect; 4) those with photosensitivity and with a repair defect distinct from that in XP-D. We present a brother and sister in the third category of TTD. Clinically, the patients have brittle hair, short stature, ichthyosis, photosensitivity, nail and dental dysplasias, cataracts, mental retardation, and pyramidal tract abnormalities. Diagnosis was made by hair mount, which shows the characteristic banding pattern with polarizing microscopy, and by hair amino acid analysis, which demonstrated decreased high-sulfur matrix proteins. Fibroblasts cultured from skin biopsies had a marked DNA excision repair defect similar to the repair defect seen in XP-D. We have documented a unique dysmyelinating disorder on magnetic resonance imaging of the brain that might explain their mental retardation, marked hyperactivity, and neurologic deficits. Following the discovery that the human excision repair cross complementing rodent ultraviolet group 2 (ERCC2) gene is able to correct the ultraviolet sensitivity of XP-D cell strains, the ERCC2 cDNA from previous TTD patients was sequenced and shows frameshifts, deletions and point mutations in the ERCC2 gene. Molecular analysis of our patients is in progress. Molecular analysis of the defects in ERCC2 in clinically distinct patients with XP,XP/Cockayne's syndrome, and TTD may provide insight into the molecular mechanisms of these genetically related but clinically distinct disorders.
毛发硫营养不良症（TTD）是一种常染色体隐性疾病，其特征为毛发硫含量缺乏且质脆，它涵盖了一组遗传性疾病，表现为高硫基质蛋白合成改变，且大多数TTD患者的成纤维细胞在紫外线损伤切除修复方面存在缺陷。与着色性干皮病（XP）患者不同，TTD患者患皮肤癌的频率并未增加。TTD患者可分为四类：1）无光敏性且紫外线损伤切除修复无缺陷者；2）无光敏性且与XP - D（互补组D）相同基因存在切除修复缺陷者；3）有光敏性且存在XP - D修复缺陷者；4）有光敏性且存在与XP - D不同的修复缺陷者。我们报告了一对属于TTD第三类的兄妹。临床上，患者有脆发、身材矮小、鱼鳞病、光敏性、指甲和牙齿发育异常、白内障、智力发育迟缓以及锥体束异常。诊断通过毛发涂片（偏振显微镜下显示特征性条带模式）和毛发氨基酸分析（显示高硫基质蛋白减少）得以确定。皮肤活检培养的成纤维细胞有明显的DNA切除修复缺陷，类似于XP - D中所见的修复缺陷。我们在脑部磁共振成像中记录到一种独特的脱髓鞘疾病，这可能解释了他们的智力发育迟缓、明显多动和神经功能缺损。在发现人类切除修复交叉互补啮齿动物紫外线组2（ERCC2）基因能够纠正XP - D细胞株的紫外线敏感性之后，对先前TTD患者的ERCC2 cDNA进行了测序，结果显示ERCC2基因存在移码、缺失和点突变。对我们患者的分子分析正在进行中。对临床上不同的XP、XP/科凯恩综合征和TTD患者中ERCC2缺陷的分子分析，可能会为这些遗传相关但临床不同的疾病的分子机制提供深入了解。
