晶状体蛋白βB1基因错义突变引起常染色体显性遗传性白内障

Missense mutation in the βB1-crystallin gene caused autosomal dominant congenital cataract in China

目的对河北汉族一个四代先天性核性常染色体显性遗传白内障家系进行基因分析,了解此家系在候选基因上是否存在突变位点。方法该家系22名成员(包括患者7人,非患者15人)知情同意进人本研究,并接受全面的眼部及全身检查,以排除白内障以及外眼部及全身疾患。该家系成员中患病者经眼部裂隙灯检查发现晶状体均为核性混浊。采集22名家系成员的外周静脉血,提取基因组DNA。选择国内外已报道的与先天性核性白内障发生相关的7个候选基因(CRYBA3/A1、CRYBB1、CRYBB2、CRYGD、GJA3、GJA8和MIP),设计引物使聚合酶链反应扩增的片段覆盖候选基因外显子,对扩增产物进行测序和序列分析,寻找突变位点。结果发现编码晶状体蛋白Βb1的基因(CRTBB1)第4外显子一个等位基因的第457个碱基发生错义突变C>A,形成杂合子,导致其编码蛋白第129位氨基酸由丝氨酸(S)转变为精氨酸(R),其余外显子的碱基序列与GenBank数据库中的正常序列一致。结论该家系的核性先天性白内障是由于CRYBB1基因外显子4的错义突变C>A引起。

Objective To observe the molecular characteristics of a four-generation Chinese pedigree with an autosomal dominant congenital cataract in Hebei province.Methods Twenty-two family members of the pedigree（including seven affected and fifteen normal individuals） agreed to participate in the study.The family members underwent ophthalmologic and general examinations to rule out any concomitant disorders.Blood samples were taken from the twenty-two family members.Candidate genes（CRYBA3/A1,CRYBB1,CRYBB2,CRYGD,GJA3,GJA8 and MIP） were PCR amplified and screened for mutations on both strands using direct sequencing.Results Sequencing of the coding regions and flanking intronic sequences of CRYBB1 showed the presence of a missense mutation that caused heterozygous transvertion（S129R） in exon 4.The change in S129R is predicted in the Beta crystallin ＂Greek key2＂ and would be expected to disrupt the three-dimensional structure of protein and β-crystallin interactions.Conclusion This is the first d.ocument of a mutation in beta crystallin that caused change in ＂Greek key2＂.A missense mutation S129R of the CRYBB1 gene caused the autosomal dominant congenital nuclear cataract.