我国汉族常染色体显性遗传性白内障一家系的基因突变分析  

Analysis on gene mutations in a Chinese pedigree with autosomal dominant inheritance cataract

作　　者：严明[1] 周新[2] 陈永梅[2] 马俊婕[2] 熊陈岭[2] 程小欢[2] 

机构地区：[1]武汉大学中南医院眼科,430071 [2]武汉大学中南医院基因诊断中心,430071

出　　处：《中华眼科杂志》2009年第8期693-698,共6页Chinese Journal of Ophthalmology

基　　金：湖北省自然科学基金（2008CDB114）作者单位：

摘　　要：目的寻找一个我国汉族常染色体显性遗传性白内障家系的致病基因。方法病例对照研究。收集家系的资料，用裂隙灯显微镜检查家系成员的晶状体；提取家系中参与研究的26名成员的基因组DNA，进行白内障致病基因（如晶状体蛋白基因和Cx基因等6个基因）外显子区域的突变扫描，用限制性片段长度多态性分析技术（PCR—RFLP）对检测到的突变进行验证，在42例年龄相关性白内障患者和204名正常人中检测是否存在已筛查到的突变。结果疾病的表型为粉尘状核性白内障；在CxS0基因（GJA8）的编码核苷酸序列第827位发现一个C到T的新突变，导致在cx氨基酸序列的276位出现一个丝氨酸到苯丙氨酸的改变，氨基酸由极性中性氨基酸变成疏水性的非极性氨基酸。在42例年龄相关性白内障患者和204名正常人中均未检测到这一突变，同时在晶状体蛋白和cx基因上发现4个单核苷酸多态性位点。结论在一个我国汉族显性遗传性白内障家系中发现一个GJA8基因的新突变（P．276S〉F），可能是该遗传性白内障的致病基因突变。Objective The aim of this study was to reveal the genetic defect of the autosomal dominant inheritance cataract in a Chinese pedigree. Methods Case-control study. There were 26 individuals investigated with clinical examination in a Chinese four generations pedigree. The genome DNA of the individuals was extracted by the improved NaI method. The exons of six cataract candidate genes in 204 normal controls and 42 senile cataract patients were screened for the mutation by PCR restriction fragment length polymorphism （PCR-RFLP） methods. Results The phenotype of the cataract was pulverulent nuclear cataract. A novel C/T transition at nucleotide position 827 was identified in the GJA8 gene that led to a serine to phenylalanine change in coden 276. This mutation was not found in 42 senile cataract patients and in 204 controls. Four single nucleotide polymorphisms （SNPs） were also found in a cataract candidate gene in the family members. Conclusions A novel GJA8 gene mutation was found in a Chinese autosomal dominant inheritance cataract pedigree. A substitution, C276T in GJA8 gene, was identified as the most likely causative mutation underlying the phenotype of pulverulent nuclear cataract in all affected family members.

关 键 词：白内障 系谱 眼蛋白质类 连接蛋白类 晶体蛋白质类 突变 

分 类 号：R686[医药卫生—骨科学]