Clinical symptoms and molecular basis of group A xeroderma pigmentosum

A组着色性干皮病的临床症状和分子基础

基本信息

批准号：
06454309
负责人：
TAMAI Hiroshi
金额：
$ 2.24万
依托单位：
Osaka Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06454309/
关键词：
Xeroderma pigmentosum DNA nucleotide excision repair A群色素性乾皮症 DNA修復蛋白質 XPA蛋白質 ERCC1蛋白質 yeast two-hybrid system E-cluster region フィルターバインデイングアッセ-DNA結合能 DNA修復活性酸素消去酵素 XPAC蛋白 RNA解析 DNA診断

项目摘要

The molecular basis of group A xcroderma pingmentosum (XP) was investigated by Southern blot analysis of genomic DNA for allelic heterogeneity in group A XP and comparison of clinical symptoms and severity of neurological complications. As previously reported, two group A XP patients (XP-YK and XP-HH) with mild skin lesions and minimal neurological abnormalities had different mutations, one was a homozygote for the nonsense mutation of exon 6 (XP'-YK), while the other was a compound heterozygote for the splicing mutation of intron 3 and the nonsense mutation of exon 6 (XP-HH). The present study revealed that one typical group A XP patient with severe skin lesions and severe neurological complications also was a compound heterozygote for the splicing mutation of intron 3 and the nonsense mutation of exon 6, thus suggesting the nonsense mutation of exon 6 is not always associated with mild skin lesions nor mild neurological manifestations. Further investigation of the sensitivity to UV radiation of fibroblasts from two atypical group A XP patients (XP-YK and XP-HH) with mild skin lesions and minimal neurological abnormalities showed intermediate post-UV colony-forming ability between that of typical group A and group C XP patients. These results suggest that DNA abnormalities are not always consistent with the severity of clinical symptoms, and that mild clinical symptoms may be explained by the residual ability of the cells to repair UV-damaged DNA.

通过Southern印迹分析基因组DNA分析了A组A组的等位基因异质性，并比较了神经系统并发症的临床症状和严重程度，研究了A组Xcroderma pingmentosum（XP）的分子基础。如前所述，两名A组XP患者（XP-YK和XP-HH）具有轻度的皮肤病变和最小的神经系统异常具有不同的突变，一个是外显子6（XP'-YK）无义突变的纯合突变，而另一种是内含型H和Nonssense sensensesssense突变的复合杂合子突变（XP'-YK）的突变。本研究表明，一个典型的A组A XP患者患有严重的皮肤病变和严重的神经系统并发症，也是内含子3的剪接突变和外显子6的无意义突变的复合杂合子，因此表明外显子6的胡言乱语突变并不总是与轻度皮肤病变相关，也不总是与轻度神经病变相关。进一步研究来自两名非典型A组A XP患者（XP-YK和XP-HH）的成纤维细胞的敏感性，具有轻度的皮肤病变和最小的神经系统异常，显示出典型的C组A组和C组XP XP患者之间的中间UV后群落形成能力。这些结果表明，DNA异常并不总是与临床症状的严重程度一致，并且可以通过细胞修复紫外线受损的DNA的残留能力来解释轻度的临床症状。