一角膜营养不良家系的TGFBI基因突变  

Pathogenic mutation of TGFBI gene in a family with corneal dystrophy

作　　者：宋晓东 吴秋月 朱培冉 刘雪艳 周宏健 李卫巍 夏欣一 SONG Xiaodong;WU Qiuyue;ZHU Peiran;LIU Xueyan;ZHOU Hongjian;LI Weiwei;XIA Xinyi(School of Medicine,Jiangsu University,Zhenjiang 212013,Jiangsu;PLA Research Institute of Clinical Laboratory Medicine,Nanjing General Hospital of Nanjing Military Region,Nanjing 210002,Jiangsu;Department of Laboratory Medicine,Lianyungang First People′s Hospital,Lianyungang 222000,Jiangsu,China)

机构地区：[1]江苏大学医学院,江苏镇江212013 [2]中国人民解放军东部战区总医院全军临床检验医学研究所,南京210002 [3]连云港市第一人民医院检验科,江苏连云港222000

出　　处：《临床检验杂志》2023年第3期176-179,共4页Chinese Journal of Clinical Laboratory Science

基　　金：国家临床重点专科军队建设项目(2014ZDZK003-3);2016年科教强卫医学重点人才(ZDRCA2016097)。

摘　　要：目的对一角膜营养不良家系的致病基因进行检测,明确该家系角膜营养不良的致病基因突变位点。方法采集先证者及其家系成员外周血标本,提取基因组DNA,采用全外显子组测序筛查先证者致病基因及突变位点,并通过Sanger测序对先证者及其家系成员DNA样本进行验证。结果全外显子测序结果显示,先证者5号染色体上的转化生长因子β诱导基因(TGFBI)4号外显子发生c.370 C>T(p.R124C)杂合突变,8号外显子发生c.1007 A>T(p.E336V)杂合突变。Sanger测序验证发现患者父亲及家系其他患者TGFBI基因也发生c.370 C>T(p.R124C)杂合突变,患者母亲及家系其他正常成员未见TGFBI基因发生突变。TGFBI基因c.370 C>T(p.R124C)突变与疾病表型共分离。结论TGFBI基因c.370 C>T(p.R124C)杂合突变是导致该家系角膜营养不良的致病原因。Objective To detect the pathogenic genes of a family with corneal dystrophy,and identify the mutation sites of the pathogenic genes.Methods The peripheral blood samples from the proband and his family members were collected,and genomic DNA was extracted.The pathogenic genes and mutation sites of the proband were screened by whole exome sequencing(WES),and the DNA of the proband and his family members were verified by Sanger sequencing.Results The results of WES showed that the proband had a c.370 C>T(p.R124C)heterozygous mutation in exon 4 and a c.1007 A>T(p.E336V)heterozygous mutation in exon 8 of the TGFBI gene on chromosome 5.Sanger sequencing found that the patient′s father and other patients in the family also had a c.370 C>T(p.R124C)mutation in the TGFBI gene.No any mutation of the TGFBI gene was detected in the patient′s mother and normal members of the family.It was indicated that the c.370 C>T(p.R124C)heterozygous mutation of the TGFBI gene was co-segregated with the disease phenotype.Conclusion The heterozygous mutation of c.370 C>T(p.R124C)in the TGFBI gene may be the pathogenic mutation of corneal dystrophy in the family.

关 键 词：角膜营养不良 转化生长因子β诱导基因 全外显子组测序 Sanger测序 

分 类 号：R446[医药卫生—诊断学] R77[医药卫生—临床医学]