Trichothiodystrophy: clinical spectrum, central nervous system imaging, and biochemical characterization of two siblings.
Trichothiodystrophy: clinical spectrum, central nervous system imaging, and biochemical characterization of two siblings.
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毛发硫营养不良：两个兄弟姐妹的临床谱、中枢神经系统成像和生化特征。
DOI：
10.1111/1523-1747.ep12399493
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Price,VH
中科院分区：
文献类型：
--
作者：
Chen,E;Cleaver,JE;Weber,CA;Packman,S;Barkovich,AJ;Koch,TK;Williams,ML;Golabi,M;Price,VH
毛发硫营养不良（TTD）是一种常染色体隐性遗传疾病，其特征是硫缺乏性脆性毛发，确定了一组遗传性疾病，其中高硫基质蛋白的合成改变和大多数TTD患者成纤维细胞中紫外线损伤的切除修复缺陷。与着色性干皮病（XP）患者相比，TTD患者的皮肤癌发生率并没有增加。TTD患者可分为四类：1）无光敏性且无UV损伤切除修复缺陷的患者; 2）无光敏性且在与XP-D相同的基因中具有切除修复缺陷的患者（互补组D）; 3）具有光敏性且具有XP-D修复缺陷的患者; 4）具有光敏性且具有与XP-D不同的修复缺陷的患者。我们提出了一个兄弟姐妹在第三类TTD。临床上，患者有头发脆，身材矮小，鱼鳞病，光敏性，指甲和牙齿发育不良，白内障，智力低下和锥体束异常。诊断是由头发安装，这表明与偏光显微镜的特征带型，并通过头发氨基酸分析，这表明减少高硫基质蛋白。从皮肤活检组织培养的成纤维细胞有明显的DNA切除修复缺陷，类似于在XP-D中看到的修复缺陷。我们已经记录了一个独特的髓鞘形成障碍的磁共振成像的大脑，可能解释他们的智力迟钝，明显的多动症，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（ERCC 2）基因能够校正XP-D细胞株的紫外线敏感性之后，对来自先前TTD患者的ERCC 2 cDNA进行测序，并显示ERCC 2基因中的移码、缺失和点突变。对病人的分子分析正在进行中。对临床上不同的XP、XP/Cockayne综合征和TTD患者中ERCC 2缺陷的分子分析可能提供对这些遗传相关但临床上不同的疾病的分子机制的深入了解。
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 patitnes with XP, XP/Cockayne's syndrome, and TTD may provide insight into the molecular mechanisms of these genetically related but clinically distinct disorders.