CRYGD基因突变与一中国先天性核性白内障家系致病相关  

A c.C70A Mutation in CRYGD is Associated with Congenital Cataract in a Chinese Family

作　　者：沈惠萍[1] 朱益华[1] 方丽君[2] 翁景宁[2] 阳菊华[3] 

机构地区：[1]福建医科大学第一临床医学院眼科,福州350005 [2]福建医科大学附属协和医院眼科,福州350001 [3]福建医科大学医药生物工程中心,福州350005

出　　处：《福建医科大学学报》2013年第2期89-92,共4页Journal of Fujian Medical University

基　　金：福建省自然科学基金(2010J06010);福建省高校跨世纪优秀人才项目(JA10127);福建医科大学教授学术发展基金(JS12003)

摘　　要：目的对一先天性核性白内障家系进行候选致病基因的筛查,以明确其发病分子基础。方法以家系先证者基因组DNA为模板,聚合酶链反应(PCR)扩增10个白内障候选致病基因的突变热点区域,PCR产物纯化后进行直接DNA测序筛查突变位点。如发现疑似突变位点,则利用直接DNA测序法对该突变位点在家系其他成员的存在情况进行疾病表型与致病突变共分离分析,进一步确认其是否为致病性突变位点。结果该家系三代呈常染色体显性遗传,临床表型大致相同,可确诊为先天性核性白内障。候选致病基因筛查发现在患者的CRYGD基因外显子2发现一个杂合突变c.C70A,正常家系成员无此突变,临床表型与基因型共分离。该突变为错义突变,导致一个CRYGD蛋白第24位的脯氨酸被苏氨酸取代(p.P24T)。结论 CRYGD(p.P24T)突变是导致该先天性核性白内障家系的致病分子基础。Objective To identify the underlying genetic defect in a Chinese family with congenital cataract. Methods The family members were recruited and underwent a full clinical examination. The thirteen exons as mutation hotspots from ten cataract-causing genes （CRYAA, CRYAB, CRYBA1, CRYBB2, CRYGC, CRYGD, GJA3, GJAS, HSF4 and PITX3） were PCR amplified and sequenced directly. When any interesting sequence variations suggestive of a mutation were found in the proband, they were later confirmed in parents and available relatives. Results The pedigree showed that the nuclear cataract is inherited as autosomal dominant trait. Sequence analysis of the coding regions of CRYGD revealed a known heterozygous c. CTOA mutation, which changed proline to threonine at position 24 of the coding region of CRYGD （p. P24T）. The mutation was segregated with the phenotype of all af- fected family members, and was not observed in the unaffected family members. Conclusion CRYGD p. P24T mutant was responsible for the pathogenicity defect of the family members with congenital nuclear cataract.

关 键 词：白内障 基因 突变 晶体蛋白质类 染色体 人 系谱 中国 

分 类 号：R776.1[医药卫生—眼科]