一个角膜营养不良家系TGFBI基因的突变分析  

Analysis of TGFBI gene mutation in a pedigree affected with corneal dystrophy

作　　者：舒安利 黎根 罗海 贺娟 胡晓雯[2] 孙嘉仪 青颖 高凌寒[2] 张娟[2] 杨超[2] 贺林[2] 万春玲 Shu Anli1 , Li Gen2 , Luo Hai1 ,He Juan1, Hu Xiaowen2, Sun Jiayi2, Qing Ying2, Gao Linghan2, Zhang Juan2, Yang Chao2, He Lin2, Wan Chunling1(1.Hunan University of Medicine, Huaihua, Hunan 418000, China ;2. Bio-X Institute, Shanghai Jiaotong University, Shanghai 200030, China)

机构地区：[1]湖南省怀化市湖南医药学院,418000 [2]上海交通大学Bio-X研究院,200030

出　　处：《中华医学遗传学杂志》2018年第5期672-674,共3页Chinese Journal of Medical Genetics

基　　金：湖南省教育厅科学研究项目（15C0995,12B102）;怀化市科技计划项目（2012-12）

摘　　要：目的分析1个先天性角膜营养不良家系的致病基因突变，探讨其分子发病原因。方法通过对2例患者DNA样本进行全外显子测序，筛选2例患者共有的突变位点，进而确定该角膜营养不良家系的候选致病基因。通过Sanger测序对13名家系成员候选突变位点进行表型共分离验证。结果Sanger测序结果显示家系8例患者均检测到TGFBI基因c．1877A〉C（p．His626Pro）杂合突变，5名正常家系成员和100名正常对照均未检测到该突变，TGFBI基因c．1877A〉C突变与该家系患者完全共分离。SIFT、PolyPhen-2和Muration Taster软件评估c．1877A〉C错义突变位点分别是“有害”、“很可能损伤”和“致病”。结论TGFBI基因c．1877A〉C突变为该先天性角膜营养不良家系的致病原因。Objective To detect potential mutation in a large Chinese pedigree affected with congenital corneal dystrophy. Methods Two patients from the pedigree were subjected to whole exome sequencing to determine the candidate gene. Suspected mutation was verified in 13 additional members by directional Sanger sequencing. Ccorrelation between genotype and phenotype was explored. Results A missense mutation, c. 1877A〉C （p. His626Pro）, was detected in exon 14 of the TGFBI gene in 8 patients from the pedigree, but not in five unaffected members and 100 unrelated healthy controls. Respectively, the mutation was predicted as ＂affecting protein function＂, ＂probably damaging＂ and ＂disease causing＂ by SIFT, PolyPhen-2 and MutationTaster. Conclusion The c. 1877A〉C mutation of the TGFBI gene probably underlies the disease in this pedigree.

关 键 词：角膜营养不良 全外显子测序 Sanger测序 TGFBI基因 

分 类 号：R440[医药卫生—诊断学] R772.2[医药卫生—临床医学]