常染色体显性先天性后极性白内障一家系晶状体蛋白基因突变分析  

Analysis of mutation for human crystallin gene in a Chinese family with autosomal dominant congenital posterior polar cataracts

作　　者：张翠[1] 张静[1] 蒋卫军[1] 李天赋 周青[2] 安丽梅[2] 李卫巍[2] 吴秋月[2] 崔英霞[2] 薛春燕[3] 张双全[1] 夏欣一[1,2] 许豪勤 许晓风[1] 

机构地区：[1]南京师范大学生命科学学院,南京210023 [2]南京军区南京总医院全军检验医学研究所,南京210002 [3]南京军区南京总医院眼科,南京210002 [4]江苏省计划生育科研所,南京210029

出　　处：《临床检验杂志》2015年第1期33-36,共4页Chinese Journal of Clinical Laboratory Science

基　　金：江苏省自然科学基金(BK2011660);江苏省科技厅省级科技专项(BM2013058)

摘　　要：目的检测一个常染色体显性先天性后极性白内障家系的晶状体蛋白（CRYAB）基因突变,并分析其与白内障的关系。方法收集该家系患者及健康者外周血标本并抽提基因组DNA。通过PCR扩增及DNA测序对常染色体显性先天性后极性白内障患者的23个候选基因进行筛选,并以体检健康者作为健康对照。用Prot Scale和Prot Param在线软件比较分析野生型和突变型αB-晶状体蛋白结构与功能,结合患者临床数据和裂隙灯照片进行综合分析。结果家系中所有患者8~10岁开始出现视力下降,均在晶状体后极存在单一且界限清晰的混浊,直径0.5~3 mm。DNA测序证实患者携带全新的CRYAB杂合错义突变（c.59C〉G）,导致氨基酸P20R的改变。该家系中健康人和200例体检健康者未发现此突变,排除单核苷酸多态性（SNPs）的可能。生物信息学软件分析结果表明P20R突变改变了αB-晶状体蛋白的生化性质。结论从一个家系常染色体显性先天性后极性白内障中发现了CRYAB杂合错义突变（c.59C〉G,p.P20R）,此突变与先天性白内障相关。Objective The purpose of this study was to identify the disease-causing gene in a family with autosomal dominant congenital posterior polar cataracts. Methods The clinical data of the family were collected and the phenotypes of lens of affected family mem- bers were recorded by slit lamp photography. Genomic DNA was isolated from peripheral blood using TIANamp DNA Blood Mini Kits. Twenty-three mutational associated hot spots with autosomal dominant congenital posterior polar cataracts were screened by PCR-based DNA sequencing. The properties and structural models of wild-type and mutant alpha-B （orB）-crystallin （CRYAB） were generated and analyzed using ProtScale and ProtParam. Results All the affected members in this family started to exhibit poor vision at the age of 8 to 10 years. The lens opacity consisted of a single, well-defined plaque with diameter of 0.5 to 3 mm, which was confined to the poste- rior pole of lens. DNA sequencing analysis of the affected members showed a novel, heterozygous missense mutation c. 59C 〉 G （P20R） in exon 1 of CRYAB gene. This mutation was not found in 10 unaffected members of the family and 200 unaffected and unrelated individuals, thereby excluding the possibility that it is a rare polymorphism. Data generated from ProtScale and ProtParam programs revealed that the mutation altered the biochemical properties of the ctB-crystallin protein. Conclusion This study reported a novel c. 59C 〉 G （P20R） missense mutation at CRYAB gene in a family with posterior polar cataract.

关 键 词：白内障 人晶状体蛋白基因 P20R突变 

分 类 号：R776.1[医药卫生—眼科]