【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。更多还原

【Abstract】 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 members 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( αB)-crystallin( CRYAB) were generated and analyzed using Prot Scale and Prot Param. Results All the affected members in this family started to exhibit poor vision at the age of 8to 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 posterior pole of lens. DNA sequencing analysis of the affected members showed a novel,heterozygous missense mutation c. 59 C > 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 Prot Scale and Prot Param programs revealed that the mutation altered the biochemical properties of the αB-crystallin protein. Conclusion This study reported a novel c. 59 C > G( P20R) missense mutation at CRYAB gene in a family with posterior polar cataract.更多还原