一个后极性白内障家系致病基因的筛查与鉴定

Screening and identification of genetic defect with congenital posterior polar cataract in a Chinese family

目的对中国一个具有常染色体显性遗传特点的后极性白内障家系进行致病基因的筛查。方法分别采集家系成员外周静脉血,提取基因组DNA,根据临床表型选取6个候选基因(CRYAA、CRYAB、PITX3、CHMP4B、MIP、CRYGD)设计引物,通过PCR扩增DNA片段,琼脂糖凝胶电泳分离DNA片段,直接测序法寻找致病基因及突变位点。结果该家系符合常染色体显性遗传家系特征,先证者表型为后极性白内障,通过候选基因外显子直接测序,发现家系内患者CRYGD基因第2个外显子第127位碱基有1个T→C的点突变,此突变导致蛋白第43位的色氨酸被精氨酸取代(W43R)。结论 CRYGD基因c.T127C(p.W43R)突变是该后极性白内障家系的致病原因。

Objective To explore the disease locus and causative mutation for autosomal dominant congenital posterior polar cataracts in a Chinese family.Methods Peripheral blood samples were collected and genomic DNA were extracted.Six candidate genes（CRYAA,CRYAB,PITX3,CHMP4 B,MIP,CRYGD） were chosen to design primers according to the clinical phenotype.After genomic polymerase chain reaction（PCR） performed,the coding exons and their flanking intronic sequences of four candidate genes were sequenced.Results Phenotype of the proband was presented as posterior polar cataract.Sequencing of the coding regions of the CRYGD gene showed the presence of a heterozygous T→C transversion at nucleotide 127 in exon 2 of CRYGD that was associated with cataracts.The missense mutation segregated with congenital posterior polar cataract.Conclusion A heterozygous mutation of CRYGD c.T127C（p.W43R） is responsible for the autosomal dominant congenital coralliform cataract in a twogeneration Chinese pedigree.;