一个先天性核性白内障家系的γ晶状体蛋白基因筛查.docVIP

中文摘要 目的：在一个先天性核性白内障家族进行家系分析和γ晶状体蛋白基因筛查，探讨基因与该家族发病的相关性。 方法：通过系谱分析，确定该先天性白内障家族遗传特征。提取基因组DNA，选择性扩增γ晶状体蛋白基因A-D（CRYGA、CRYGB、CRYGC、CRYGD），运用直接测序的方法检查基因序列。通过构象敏感性凝胶电泳（CSGE）的方法在95个正常对照中筛查发现的核苷酸。 结果：该家族为常染色体显性遗传家系。患者以出生就发生的核性晶状体混浊和眼球震颤为特征，并随时间发展进行性加重。在该家族中发现了九种核苷酸序列改变，它们分别是：CRYGA的36-21GA、443TC、CRYGB的9-36-37insC、192CT、331CA、CRYGC的252+21TG和CRYGD的51TC、252+30TC、570CT。这些核苷酸改变都没有该家族疾病共分离。其中，443TC导致了γA晶状体蛋白148位密码子的亮氨酸变成了脯氨酸（L148P），331CA造成γB晶状体蛋白111位密码子的亮氨酸变成异亮氨酸（L111I）。CSGE筛查发现在正常对照中这两种。 结论：该家系为呈常染色体显性遗传的先天性核性白内障家系。γ晶状体蛋白基因初步排除γ晶状体蛋白基因与该先天性白内障家族有关。该家族白内障的发生可能由其他位置的基因变异引起。 关键词：先天性白内障基因筛查γ晶状体蛋白基因 Abstract Aim: Through pedigree analysis of a congenital cataract family and screening of the γ-crystallin genes in the family, explore the association between the genes and the disease in this family. Methods: Confirm the inheritance character of the family by pedigree analysis. Extract the genomic DNA and amplify the CRYGA, CRYGB, CRYGC, CRYGD genes. The genes were sequenced directly. The nucleotide alternations which were found to lead to amino acid variance were screened by conformation sensitive gel electrophoresis (CSGE) and sequencing in 95 controls. Result: It’s autosomal dominant inheritance in this family. The affected individuals are characterized by nuclear cataract and nystagmus present at birth and progress with time. Nine sequence variances were found in this family: 36-21GA and 443TC in CRYGA, 9-36-37insC, 192CT and 331CA in CRYGB, 252+21TG in CRYGC, 51TC, 252+30TC and 252+82CTin CRYGD. No nucleotide alternations were identified as cosegregating with the disease. Two nucleotide variances lead to amino acid substitutions: L148P in polypeptides of γA-crystallin and L111I in polypeptides of γB-crystallin, respectively. These amino acid alternations were also found in the control group. The frequencies show no significant difference between the family and the control. Conclusion: It’s an autosomal dominant congenital nuclear cataract family. Nine sequence alternations of CRYG g