先天性白内障一家系的致病基因研究  

Gene mutation analysis of a Chinese family with congenital cataract

作　　者：郑青青[1] 李文伟[1] 沈婷[2] 洪朝阳[1] 

机构地区：[1]温州医科大学附属眼视光学院,325000 [2]浙江省人民医院眼科中心

出　　处：《浙江医学》2015年第3期189-192,196,共5页Zhejiang Medical Journal

基　　金：浙江省卫生厅科技项目(2010KYA019)

摘　　要：目的对一个来自浙江省杭州地区的三代先天性白内障家系进行常染色体显性遗传基因的突变分析,以寻找其可能的致病基因及突变位点。方法该家系共10例成员,其中包括4例患者。10例家系成员在浙江省人民医院眼科中心接受眼科专科检查及全身检查,以排除存在白内障以外的眼部及全身疾患。10例家系成员各抽取外周血5ml,提取基因组DNA。针对国内外文献报道的与常染色体显性遗传先天性白内障相关的18个基因(CRYAA、CRYAB、CRYBA1、CRYBA2、CRYBA4、CRYBB1、CRYBB2、CRYGC、CRYGD、CRYGS、GJA3、GJA8、MIP、BFSP、HSF4、PITX3、EPHA2、PAX6)设计引物,进行PCR扩增,对扩增产物进行测序和序列分析,了解这10例家系成员的以上基因是否存在相应的序列。结果临床眼科检查显示该家系先天性白内障类型为粉尘状白内障。候选基因序列测定显示在CRYAA第1个外显子中第6位碱基发生C→T置换,氨基酸同为天门冬氨酸。该家系中所有患者均有此改变,而所有的正常家系成员均无此改变。结论CRYAA第1个外显子中第6位碱基发生C→T的同义突变可能是导致该家系先天性白内障发生的致病原因。Objective To identify the pathogenic gene of congenital cataract in a Chinese family. Methods In a three- generation Chinese family 4 members were affected by congenital cataract in both eyes. Ten individuals from this family underwent ophthalmologic and physical examination in Zhejiang Provincial People＇s Hospital. The DNA was extracted from pe-riphery blood samples and amplified by PCR. The PCR products were sequenced and analyzed to detect mutations of 18 autoso-mal dominant congenital contact- related genes （CRYAA, CRYAB, CRYBA1, CRYBA2, CRYBA4, CRYBB1, CRYBB2, CRYGC, CRYGD, CRYGS, GJA3, GJA8, MIP, BFSP, HSF4, PITX3, EPHA2 and PAX6）. Results The congenital cataract in this family is pulverulent type. A C→T mutation at 6 base in the first exon of CRYAA gene was detected, which was coding the same amino acid （asparaginic acid）. Al the patients in this family had this mutation, while the mutation was not detected in normal family mem-bers. Conclusion The study identifies a mutation in CRYAA, which may contribute to the pathogenesis of congenital cataract in this family.

关 键 词：先天性白内障 基因突变 晶状体蛋白基因 

分 类 号：R776.1[医药卫生—眼科]