Two new XPD patients compound heterozygous for the same mutation demonstrate diverse clinical features
Two new XPD patients compound heterozygous for the same mutation demonstrate diverse clinical features
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DOI：
10.1111/j.0022-202x.2005.23745.x
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发表时间：
2005-07-01
影响因子：
6.5
通讯作者：
Lehmann, AR
中科院分区：
文献类型：
--
作者：
Fujimoto, M;Leech, SN;Lehmann, AR
着色性干皮病（XP）和Cockayne综合征（CS）都是罕见的常染色体隐性遗传疾病，DNA修复缺陷。它们通常在临床和遗传上都是不同的，但在极少数情况下，患者同时表现出两种疾病的临床特征。我们报告了两个新的表型不同的情况下，XP与CS（着色性干皮病和Cockayne综合征交叉综合征（XP/CS））携带相同的突变（G47 R）的蛋白质的N末端内的XPD基因的额外功能。两例患者均具有XP和CS的临床特征，但只有一例符合大多数诊断CS的标准。不寻常的是，患者1发生了早期皮肤癌，而患者2从未发生任何恶性肿瘤。来自这两个患者的细胞具有着色性干皮病互补组D（XPD）细胞的典型修复缺陷，但也具有在XPD/CS细胞中特异性发现的不受控制的DNA断裂的表型，并且类似地降低了TFIIH水平。尽管我们的两名患者之间存在这些相似之处，但他们的临床特征却截然不同，临床严重程度与紫外线照射的其他细胞反应相关。
Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are both rare autosomal recessive disorders with defects in DNA repair. They are usually distinct both clinically and genetically but in rare cases, patients exhibit the clinical characteristics of both diseases concurrently. We report two new phenotypically distinct cases of XP with additional features of CS (xeroderma pigmentosum and Cockayne syndrome crossover syndrome (XP/CS)) carrying an identical mutation (G47R) in the XPD gene within the N terminus of the protein. Both patients had clinical features of XP and CS but only one fulfilled most criteria for diagnosing CS. Unusually, patient I developed early skin cancer, in contrast to patient 2, who never developed any malignancies. Cells from both these patients have repair defects typical of xeroderma pigmentosum complementation group D (XPD) cells, but also had the phenotype of uncontrolled DNA breakage found specifically in XPD/CS cells and similarly reduced levels of TFIIH. Despite these similarities between our two patients, their clinical features are quite different and the clinical severity correlates with other cellular responses to ultraviolet irradiation.