中国北方一先天性白内障家系GJA8基因新突变

New mutation of GJA8 gene in a family with congenital cataract in northern China

目的对一个中国先天性白内障家系进行分子遗传学研究,并分析其基因型与表型相关性。方法对该家系采集详细的病历资料,并进行全面的眼科检查,采集外周血并提取DNA。用二代测序方法对可能致病基因进行测序,对发现的变异通过Sanger测序法进行DNA序列分析。结果在先证者的GJA8基因第二外显子中发现了一个杂合错义突变[c.199G>T](p.Asp67Tyr),这一突变也存在于该家系的其他白内障成员中,在正常亲属中未发现相同改变。该家系先证者IV2表现为双眼晶状体全白色混浊,其母III3表现为双眼点状晶状体混浊。结论在一个中国先天性白内障家系中,发现GJA8基因新致病突变(c.199G>T),拓宽了GJA8基因的突变谱,有助于加深对先天性白内障发病机制的认识。

Objective To study the molecular genetics in a Chinese family with congenital cataract and to describe its genotype-phenotype correlation.Methods Detailed clinical materials were collected and a comprehensive ophthalmological examination was conducted with the family.Peripheral blood was collected and DNA was extracted.The possible pathogenic genes were sequenced by next-generation sequencing(NGS),and the mutations were performed by Sanger sequencing.Results A heterozygous missense mutation [c.199 G>T](p.Asp67 Tyr) was found in the second exon of the proband’s GJA8 gene.The mutation also exists in other family members with cataract,but no similar changes in normal relatives.The proband Ⅳ2 presented total opacity of the binocular lens and his mother Ⅲ3 showed punctate opacity of the binocular lens.Conclusion Our findings provide a new pathogenic mutation of GJA8(c.199 G>T) in a Chinese family with congenital cataract,which widened the mutation spectrum of GJA8 gene and helped to deepen the understanding of the pathogenesis of congenital cataract.