颗粒状角膜营养不良家系的BIGH3基因突变  

Exon 12 of BIGH3(R555W) Mutation in Granular Corneal Dystrophy in a Chinese Kindred

作　　者：阳菊华[1] 童绎[2] 朱益华[2] 肖继勇 陈贻锴[1] 林建银[4] 

机构地区：[1]福建医科大学医药生物工程中心,福州350004 [2]福建医科大学附属第一医院眼科,福州350005 [3]南平市第一医院眼科,南平353000 [4]福建医科大学分子医学研究中心,福州350004

出　　处：《福建医科大学学报》2007年第1期14-16,共3页Journal of Fujian Medical University

基　　金：福建省自然科学基金资助项目(C0510009);福建医科大学科学研究发展基金资助项目(FJGXY04020)

摘　　要：目的以基因突变分析一角膜营养不良家系的致病分子基础。方法应用PCR产物直接DNA测序及限制性内切酶分析检测家系中7例患者和6例表型正常成员的K3、K12和BIGH3基因突变情况。结果该家系患者成员在K3与K12基因的编码序列区没有发现突变,而BIGH3基因外显子12存在CGG>TGG(R555W)突变杂合子,家系表现正常成员及正常对照均无BIGH3基因突变;限制性内切酶分析结果显示突变与疾病表现型呈完全共分离。结论利用基因突变分析确诊我国首例报道的Meesmann角膜营养不良家系属于颗粒状角膜营养不良,且为BIGH3 R555W杂合突变类型。Objective Molecular genetic analysis of a large Chinese corneal dystrophy kindred. Methods Thirteen individuals including seven affected and six unaffected family members in this granular corneal dystrophy kindred were studied. Genomic DNA was purified from blood peripheral leukocytes. All of the exons of both the Keratin3 and the keratin12 genes, and the exon 4 and exon 12 of BIGH3 gene were amplified using polymerase chain reaction（PCR）, followed by direct bidirectional sequencing for mutation detection. The mutation was confirmed by restriction digest analysis. Results Direct sequencing of the patients＇ genomic DNA revealed there was no mutation in all of the exons of K3 and K12 genes, but a missense mutation（CGG〉TGG） in the exon12 of BIGH3（R555W） was found. This mutation in this family completely cosegregates with the disease phenotype. Conclusion This kindred was diagnosed with granular corneal dystrophy harbored a heterozygous R555W mutation of the BIGH3 gene.

关 键 词：角膜营养不良 遗传性 基因 突变 序列分析 DNA 聚合酶链反应 系谱 

分 类 号：R772.21[医药卫生—眼科]