两种角膜营养不良的 BIGH3基因突变研究

目的　了解中国角膜营养不良患者所存在的 BIGH3基因突变类型。方法　应用聚合酶链反应并结合 DNA测序技术 ,分别对 3例颗粒状角膜营养不良和 12例 Avellino角膜营养不良患者以及 10名正常人 BIGH3基因第 4外显子和第 12外显子进行突变检测。结果　所检测的角膜营养不良患者均存在BIGH3基因突变 ,所有正常对照无 BIGH3基因突变。其中 12例为 R12 4 H突变杂合子 ,3例为 R5 5 5 W突变杂合子。结论　颗粒状、Avellino角膜营养不良分别存在 BIGH3基因 R5 5 5 W及 R12 4 H突变 ,而 R12 4 H突变相关的 Avellino角膜营养不良在 BIGH3基因突变所导致的角膜基质营养不良中最为常见。12 4和 5 5 5密码子亦是中国角膜营养不良患者 BIGH3基因的突变热点。

Identification of BIGH3 gene mutations in the patients with two types of corneal dystrophies

ObjectiveTo identify the mutations of BIGH3 gene in Chinese patients with corneal dystrophies. MethodsPolymerase chain reaction in exon 4, exon 12 and direct DNA sequencing of BIGH3 gene were performed in fifteen patients with corneal dystrophies and ten normal individuals as controls. Results Mutations in BIGH3 gene were detected in all the patients with corneal dystrophies. BIGH3 gene mutations were not found in normal subjects. Twelve patients with Avellino corneal dystrophy had the missense mutation R124H in the BIGH3 gene. Three patients with granular corneal dystrophy had the missense mutation R555W in the BIGH3 gene. ConclusionR124H and R555W mutations in BIGH3 gene were found in the patients with Avellino and granular corneal dystrophies. Avellino corneal dystrophy associated with the R124H mutation is the most common form in the corneal dystrophies resulting from BIGH3 gene mutations. Condons 124 and 555 are also the hot spots for the mutations in the BIGH3 gene in the Chinese patients with corneal dystrophies.