| 刘 青,郭 佳,马子程,严 然,朱思泉.常染色体显性遗传性先天性白内障的基因突变研究[J].,2023,(10):1801-1808 |
| 常染色体显性遗传性先天性白内障的基因突变研究 |
| Study on Gene Mutation of Autosomal Dominant Congenital Cataract |
| 投稿时间：2023-02-18 修订日期：2023-03-13 |
| DOI：10.13241/j.cnki.pmb.2023.10.001 |
| 中文关键词: 常染色体显性遗传 先天性白内障 基因突变 |
| 英文关键词: Autosomal dominant inheritance Congenital cataract Gene mutation |
| 基金项目:国家自然科学基金项目（52073181）；国家自然科学基金项目（81441024） |
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| 中文摘要: |
| 摘要 目的：从收集的两个来自中国的常染色体显性遗传性的先天性核性白内障家系中，确定与其白内障致病相关的基因遗传突变位点，以明确致病原因。方法：首先通过记录详细的家系成员患病史、白内障手术史和其他临床资料，通过眼科常用的视力、眼压、裂隙灯检查以及眼底检查，排除家系成员的其他眼科疾病。并在取得家系成员的知情同意下，从家系成员的外周血白细胞中提取基因组DNA，最后通过对已知的先天性白内障候选基因进行测序，以筛选出致病的突变位点。并通过软件分析突变位点的高保守性。结果：通过眼科常用的裂隙灯仪器检查，两个家系的先天性白内障临床表型均被确定为核性白内障类型。通过对先天性白内障就候选基因直接测序，发现了在晶状体蛋白γD基因（CRYGD）中，核苷酸位置c.193处，发现了一个G>A的突变。该突变与两个家系中所有患病的个体共分离，未患病的成员和120名无关对照成员中未观察到该突变。共保守分析表明，一个高度保守的区域序列位于CRYGD的第65位密码子（P.65）。结论：在两个常染色体显性遗传性先天性核性白内障的中国家系中发现了CRYGD基因的一个新突变D65N，这是第一次在CRYGD基因的第193位核苷酸处，发现突变G→A。导致了第65位密码子的天冬氨酸（D）突变为天冬酰胺（N），这些结果提供了强有力的证据，证明了晶状体蛋白γD基因（CRYGD）是先天性白内障的致病基因，并与核性的先天性白内障临床表型高度相关。 |
| 英文摘要: |
| ABSTRACT Objective: To identify the genetic mutation sites related to the pathogenesis of cataract from two families with autosomal dominant congenital nuclear cataract from China. Methods: First of all, the family members' disease history, cataract surgery history and other clinical data were recorded in detail, and other ophthalmic diseases of the family members were excluded through common ophthalmic examinations such as vision, intraocular pressure, slit lamp and fundus examination. With the informed consent of the family members, the genomic DNA was extracted from the peripheral blood leukocytes of the family members, and finally the known candidate genes for congenital cataract were sequenced to screen out the pathogenic mutation sites. The high conservatism of mutation sites was analyzed by software. Results: The clinical phenotype of congenital cataract in the two families was determined as nuclear cataract by the slit lamp instrument commonly used in ophthalmology. Through direct sequencing of candidate genes for congenital cataract, it was found that crystallin γ D gene (CRYGD), a mutation of G>A was found at the nucleotide position c.193. The mutation was isolated from all diseased individuals in the two families. The mutation was not observed in the non-diseased members and 120 unrelated control members. Co-conservative analysis showed that a highly conserved region sequence was located at codon 65 (P.65) of CRYGD. Conclusion: A new mutation D65N of CRYGD gene was found in two Chinese families with autosomal dominant congenital nuclear cataract. This is the first time that the mutation G → A was found at the 193th nucleotide of CRYGD gene. This results in the mutation of aspartic acid (D) at codon 65 to asparagine (N). These results provide strong evidence that crystallin γ D gene (CRYGD) is the pathogenic gene of congenital cataract, and is highly correlated with the clinical phenotype of nuclear congenital cataract. |
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