国人BIGH3相关性角膜营养不良基因突变类型分析

Molecular genetic study on corneal dystrophy related to BIGH3 in China

目的探讨中国BIGH3基因相关性角膜营养不良患者的基因突变类型。方法从40例颗粒状、格子状、Reis-B櫣cklers角膜营养不良患者的静脉血中提取全血白细胞DNA,应用聚合酶链反应(PCR)技术,分别合成BIGH3基因第4、12、14外显子PCR产物,并对各产物进行DNA直接测序,同时行裂隙灯显微镜检查并照裂隙灯显微镜外眼像。45例正常人采集静脉血样进行对照检测。结果40例患者均检出BIGH3基因突变,其中R124H突变为22例、R555W突变6例、R124C突变5例、H626R突变5例、R124L突变2例。结论中国人与亚洲的日本和韩国人相似,在BIGH3基因相关的角膜营养不良患者中,Avellino角膜营养不良(ACD,R124H突变)最为常见。

Objective Corneal dystrophy is a heritage-related primary disease with histopathological feature. Several genetic mutations are related to different type of corneal dystrophies, and BIGH3 gene shows the close correlation with corneal dystrophy. The present work was to investigate the BIGH3 gene mutations of patients with corneal dystrophy in China. Methods Molecular genetic analysis was performed on DNA extracted from peripheral leukocytes in 40 patients with corneal dystrophy. Exons 4,12,14 of the BIGH3 gene were amplified by polymerase chain reaction and sequenced directly. The corneas of these patients were examined and photographed under the slit lamp biomicroscope,and the case history and family history from above patients were collected. Forty-five normal subjects were recruited for the molecular genetic analysis as controls. Results Mutation of BIGH3 gene occurred in all 40 patients, including R124H mutation in 22 cases with Avellino （ACD） , R555W mutation in 6 cases with granular corneal dystrophy type I （GCD I ） , R124C mutation in 5 cases with lattice corneal dystrophy type I （LCD I ）, H626R mutation in 5 cases with lattice corneal dystrophy i （LCDi）, R124L in 2 cases with Reis-Buecklers corneal dystrophy（RBCD）. Conclusion Avellino corneal dystrophy （RI24H） is the most common form of mutation in patients with corneal dystrophy in China.