A型着色性干皮病中XPAC基因的无义突变

Nonsense Mutation of XPAC Gene in a Pedigree with Xeroderma Pigmentosum Group A

目的检测国内一A型着色性干皮病家系中XPAC基因的突变。方法PCR扩增XPAC基因的全部外显子,并行DNA测序。针对所发现的突变以DdeⅠ内切酶行限制性片段长度多态性(RFLP)分析。结果PCR结合DNA测序发现患者XPAC基因第5外显子存在异常:第631位碱基由胞嘧啶突变为胸腺嘧啶,使第211位氨基酸由精氨酸变为终止密码(R211X),导致其编码的XPA蛋白缺失了C端的63个氨基酸。其父母皆为杂合子。RFLP结果证实了此突变的存在。结论本A型着色性干皮病家系中存在XPAC基因突变,突变致使XPA蛋白功能缺陷,DNA损伤的修复功能受损,导致临床上出现皮肤老化和癌变。

Objective To determine XPAC gene mutation in a Chinese pedigree with xeroderma pigmentosum group A.Methods All exons of XPAC gene were analyzed by PCR-DNA sequencing in the pedigree.The mutations were confirmed by restriction fragment length polymorphism(RFLP).Results By PCR-DNA sequencing,a nonsense mutation of C631T was identified which caused R211X substitution in exon5of XPAC gene.The mutated gene encoded a defective XPA protein truncated by63amino acids in C-terminus.The parents were all heterozygotes.The results were confirmed by RFLP.Conclusions A nonsense mutation is found in XPAC gene of a pedigree of xeroderma pigmentosum group A.This mutation may impair XPA protein function of DNA repair,and as a consequence,cause skin aging and carcinogenesis.