Molecular and cellular analysis of the DNA repair defect in a patient in xeroderma pigmentosum complementation group D who has the clinical features of xeroderma pigmentosum and Cockayne syndrome.
Molecular and cellular analysis of the DNA repair defect in a patient in xeroderma pigmentosum complementation group D who has the clinical features of xeroderma pigmentosum and Cockayne syndrome.
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DOI：
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发表时间：
1995
影响因子：
9.8
通讯作者：
B. Broughton;A. F. Thompson;S. A. Harcourt;W. Vermeulen;J. Hoeijmakers;E. Botta;M. Stefanini;M. King;C. Weber;J. Cole
中科院分区：
文献类型：
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作者：
B. Broughton;A. F. Thompson;S. A. Harcourt;W. Vermeulen;J. Hoeijmakers;E. Botta;M. Stefanini;M. King;C. Weber;J. Cole
着色性干皮病（XP）和Cockayne综合征（CS）是两种不同的遗传性疾病，它们与紫外线诱导的DNA损伤的切除修复缺陷有关。少数患者先前已描述了这两种疾病的临床特征。在本文中，我们描述了一个人在这一类谁有不寻常的细胞反应，紫外线。我们发现，他培养的成纤维细胞和淋巴细胞是非常敏感的紫外线-C照射，尽管核苷酸切除修复的水平是30%-40%的正常细胞。该缺陷被分配到XP-D互补组，我们已经确定了XPD基因中的两个致病突变：遗传自患者母亲的等位基因中第675位氨基酸的gly->arg变化和遗传自患者父亲的等位基因中第669位氨基酸的-1移码。这些突变位于760个氨基酸的XPD蛋白的C-末端20%，在我们最近发现的患有谷胱甘肽营养不良的患者中的几个突变的区域中。
Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are quite distinct genetic disorders that are associated with defects in excision repair of UV-induced DNA damage. A few patients have been described previously with the clinical features of both disorders. In this paper we describe an individual in this category who has unusual cellular responses to UV light. We show that his cultured fibroblasts and lymphocytes are extremely sensitive to irradiation with UV-C, despite a level of nucleotide excision repair that is 30%-40% that of normal cells. The deficiency is assigned to the XP-D complementation group, and we have identified two causative mutations in the XPD gene: a gly-->arg change at amino acid 675 in the allele inherited from the patient's mother and a -1 frameshift at amino acid 669 in the allele inherited from his father. These mutations are in the C-terminal 20% of the 760-amino-acid XPD protein, in a region where we have recently identified several mutations in patients with trichothiodystrophy.