摘要
目的探索采用DNA测序对河南1个5代常染色体显性遗传性核性白内障家系候选致病基因进行突变筛查和产前诊断的可行性。方法采集该家系成员的外周静脉血，提取基因组DNA。选择与先天性核性白内障发生相关的4个晶状体蛋白基因（CRYBA1／A3、CRYBB1、CRYBB2和CRYGD）作为候选基因，采用聚合酶链反应扩增候选基因的外显子及其侧翼的非编码区序列，对扩增产物进行测序和序列分析，寻找突变位点。通过孕早期绒毛采样对1名高危胎儿进行产前基因诊断。结果该家系中先证者及患者CRYBBl基因第4外显子发生c．387C〉A杂合突变，导致其编码的晶状体GB1蛋白第129位氨基酸由丝氨酸转变为精氨酸（P．S129R），行产前诊断的胎儿未携带该突变，出生后随访证实为1名健康个体。结论CRYBB1基因C．387C〉A（P．S129R）突变为该核性先天性白内障家系的致病突变，本研究完成了CRYB脚基因突变所致核性先天性白内障家系的产前基因诊断。
Objective To perform mutation screening and prenatal diagnosis for a five-generation Chinese pedigree with autosomal dominant congenital nuclear cataract from Henan province by DNA sequencing. Methods Blood samples were taken from the family members. Four candidate genes （CRYBA1/A3, CRYBB1, CRYBB2 and CRYGD）were screened for mutations using direct sequencing. Prenatal genetic diagnosis was provided for a fetus at early gestation through chorionic villus sampling. Results A missense mutation, c. 387C〉A, was detected in exon 4 of the CRYBB1 gene in all of the patients. The mutation has resulted in a p. S129R transversion. The same mutation was not found in the fetus of the proband, who was confirmed to be healthy by one-year follow-up. Conclusion A missense mutation p. S129R of the CRYBB1 gene probably underlies the autosomal dominant congenital nuclear cataract in this pedigree. Detection of the mutation also facilitated prenatal genetic testing for the family.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2013年第3期266-269,共4页
Chinese Journal of Medical Genetics
基金
基金项目：河南省卫生科技中青年科技创新人才项目
教育部留学回国人员科研启动基金资助项目
