格子状角膜营养不良患者BIGH3基因突变的研究

目的探讨中国格子状角膜营养不良(LCD)患者基因突变类型。方法对2002年7至11月来我院就诊的8例不伴有全身淀粉样物质沉积的LCD患者,自静脉血提取全血白细胞DNA,应用聚合酶链反应(PCR)技术,扩增BIGH3基因目的片段,并对其进行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。收集32名正常人静脉血样进行同样检测,作为对照。结果3例检出BIGH3基因第4外显子的R124C突变(417位点碱基C→T),呈杂合子,临床表现为典型的LCDI型;另外5例检出第14外显子的H626R突变(1924位点碱基A→G),亦为杂合子,该型临床表现介于LCDⅠ型与LCDⅢ或ⅢA型之间,为一中间类型。结论中国LCD患者中既存在引起LCDⅠ型的R124C突变,也存在H626R突变。因此,H626R突变并非是英国和法国特有的类型,也可为亚洲患者的一种基因突变类型。

Molecular genetic study on patients with lattice corneal dystrophy in China

OBJECTIVE: To investigate the mutations of the BIGH3 gene in patients with lattice corneal dystrophy in China. METHODS: Molecular genetic analysis was performed on DNA extracted from peripheral leukocytes from eight patients with lattice corneal dystrophy and without systemic amyloidosis in Tongren Ophthalmic Center. Exons 4, 12, 14 of the BIGH3 gene were amplified by polymerase chain reaction and were sequenced directly. The cornea of these patients were examined with slit lamp biomicroscope and photographed. At the same time, 32 normal subjects were recruited in the molecular genetic analysis as the controls. RESULTS: Three LCDI patients had R124C mutation (one missense mutation at position 417 C-->G of exon 4) in the BIGH3 gene, all of them were heterozygous. The other five patients showed different H626R mutations at position 1924 from A to G of the BIGH3 gene in exon 14, all of them were heterozygous too. The clinical appearance in patients with H626R mutation was an intermediate type between LCDI and LCDIII or LCDIIIA. CONCLUSIONS: R124C mutation and H626R mutation are detected in Chinese patients with lattice corneal dystrophy. It seems that H626R mutation not only presents in British and French patients, but also can be found in Asia patients.