一汉族先天性核型白内障家系的基因突变研究

Genetic Mutation Detection in a Chinese Han Nation Family with Congenital Nuclear Cataract

目的检测一汉族先天性核型白内障家系的基因突变位点。方法收集家系内患者及眼部表型正常成员外周静脉血标本并提取家系成员基因组DNA样本。采用白内障致病基因靶向捕获与高通量DNA测序技术在81个先天性白内障已定制候选致病基因panel中筛选可能致病突变。采用PCR技术扩增所有家系成员可疑突变基因外显子片段,并联合Sanger测序验证家系患者突变位点是否为该家系致病突变。结果与NCBI、HGMD专业版数据库比对,验证突变位点是否为致病突变或全新突变。结果临床表型分析表明,家系内所有患者在三岁之前均开始出现不同程度的视力下降,均呈现核型白内障表现。靶向捕获联合高通量测序检测到所有家系内患者均携带CRYAB基因的杂合错义突变(c.59C>G,p.P20R),即1号外显子第59位核苷酸碱基由胞嘧啶突变为鸟嘌呤,此突变导致第20位氨基酸残基由脯氨酸变为精氨酸,而家系内正常人不携带该突变。结论CRYAB基因杂合错义突变c.59C>G可导致先天性核型白内障的发生。

Objective To determine the pathogenic gene mutations of a Chinese family with congenital nuclear cataract.Methods Peripheral venous blood samples were obtained from normal persons and patients of this family to complete genomic DNA extraction.81 genes and areas involved in the cataract panel have been screened by gene capture sequencing technique on the DNA samples extracted from the proband of the family.Sanger sequencing was carried out to verify the mutation after comparation with HGMD database(professional version).Results Diminution of vision and lenticular opacity were presented in all patients of this family before 3 years old.A missense mutation(c.59C>G,p.P20R)was detected in CRYAB gene,which may lead to an alteration of amino acid from proline to arginine.The mutation was not detected in normal persons of this family.Conclusion Mutation of CRYAB gene can cause congenital nuclear cataract.