Thiel-Behnke角膜营养不良家系的TGFBI基因突变研究  

TGFBI gene mutation analysis in a Chinese family with Thiel-Behnke corneal dystrophy

作　　者：齐艳华[1] 赫红丹[1] 李颖[1] 王丽[1] 林辉[1] 苏虹[1] 谷静芝[1] 黄尚志[2] 

机构地区：[1]哈尔滨医科大学附属第二医院眼科, 150086 [2]中国医学科学院基础医学研究所、中国协和医科大学基础医学院

出　　处：《中华眼科杂志》2007年第8期718-721,共4页Chinese Journal of Ophthalmology

摘　　要：目的探讨我国Thiel—Behnke角膜营养不良中TGFBI基因突变的类型，了解5代常染色体显性遗传性Thiel—Behnke角膜营养不良家系的基因突变位点。方法对1个常染色体显性遗传性Thiel-Behnke角膜营养不良家系成员中10例患者和2名正常人进行眼科常规检查，抽取5ml外周血，盐析法提取基因组DNA，利用TGFBI基因第4、7、8、11、12外显子特异性引物，进行PCR扩增，对扩增产物测序进行突变检测。结果对TGFBI第4、7、8、11、12外显子扩增产物进行直接双向测序，在TGFBI基因第12外显子发现G→A的改变，此改变位于基因第12外显子，导致编码蛋白质第555位精氨酸被谷氨酰胺取代（R555Q）。这一序列的改变见于家系所有受累成员，而家系其他正常个体均无此改变。结论本研究Thiel—Behnke角膜营养不良家系患者的角膜病变由TGFBI基因R555Q突变引起，两者密切相关。Objective To identify the gene mutation in autosomal dominant Thiel-Behnke corneal dystrophy affecting a five-generation Chinese family. To study the TGFBI gene mutation in Chinese patients with Thiel-Behnke corneal dystrophy by molecular genetic analysis. Methods Ophthalmologic examinations were performed in 10 patients and two normal family members in an autosomal dominant Thiel-Behnke corneal dystrophy family. Five ml peripheral blood was collected and Genomic DNA was extracted using salt fraetionation. The exons 4, 7, 8, 11 and 12 of the TGFBI gene were amplified by PCR and mutation analysis was performed by direct sequencing. Results Mutation analysis of the exons 4, 7, 8, 11 and 12 of the TGFBI gene identified a C→A missense mutation in the exon 12 by bidirectional sequencing. This mutation resulted in a substitution of glutamine for arginine at amino acid 555 （R555Q） of the protein. This mutation existed in all of the patients, but not in unaffected individuals. Conclusion Thiel-Behnke corneal dystrophy in this family is caused by R555Q mutation of the TGFBI gene, the phenotypes of this corneal dystrophy are closely correlated with TGFBI mutation.

关 键 词：角膜营养不良 遗传学 系谱 转化生长因子β 细胞外基质蛋白质类 突变 

分 类 号：R686[医药卫生—骨科学]