格子状角膜营养不良一家系TGFBI基因的突变研究  

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

作　　者：段宏辉 郑利斌 伍海建[1] 徐德建 管涛[1] Duan Honghui, Zheng Libin , Wu Haijian , Xu Dejian , Guan Tao(Center of Ophthalmology, Taizhou Municipal Hospital, Taizhou, Zhejiang 318000, China; Key Laboratory of Biotherapy of Zhejiang Province, the Affiliated Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, Chin)

机构地区：[1]浙江省台州市立医院眼科中心,318000 [2]浙江大学医学院附属邵逸夫医院浙江省生物治疗重点实验室,杭州310006

出　　处：《中华医学遗传学杂志》2018年第4期518-521,共4页Chinese Journal of Medical Genetics

摘　　要：目的研究一个格子状角膜营养不良家系的临床特征及TGFBI基因的突变类型。方法收集该家系4代35名成员（其中患者11例）的外周血样，提取基因组DNA，应用PCR和DNA直接测序技术，对TGFBI基因17个外显子及外显子内含子拼接部进行基因变异的检测；用生物信息学软件分析基因变异对蛋白质结构和功能的影响。并对家系成员进行详细的临床检查。结果家系中所有患者TGFBI基因第4外显子存在P．R124C杂合性变异，正常成员未发现此变异，生物信息学分析P．R124C变异为已报道的TGFBI基因突变类型，该突变对蛋白质结构和功能为致病性。该家系中P．R124C突变与疾病表型共分离，呈常染色体显性遗传，结合患者的临床特征，确诊为典型格子状I型角膜营养不良。结论该格子状I型角膜营养不良家系存在TGFBI突变，为致病性P．R124C杂合性突变。基因分析为疾病明确诊断提供了可靠的依据。Objective To explore the clinical features and mutation of TGFBI gene in a Chinese pedigree affected with lattice corneal dystrophy （LCD）. Methods Genomic DNA was extracted from 35 members including 11 patients from the pedigree. The 17 exons and splicing region of introns of the TGFBI gene were amplified by PCR. The products were directly sequenced and compared with GenBank database to identify potential mutation. Bioinformatic analysis was carried out to predict the effect of mutation on proteins. Results A heterozygous mutation （p. R124C） was found in exon 4 of the TGFBI gene in all patients from the pedigree but not among unaffected members. The mode of inheritance of corneal dystrophy in this pedigree was identified as autosomal dominant. Bioinformaties analysis predicted that the p. R124C mutation may be functionally deleterious. The phenotype of corneal dystrophy in the pedigree was determined to be LCD I type. Conclusion The p. R124C mutation of the TGFBI gene probably underlies the pathogenesis of LCD in this Chinese pedigree. Genetic testing can facilitate proper diagnosis of this type of corneal dystrophy.

关 键 词：角膜营养不良 TGFBI基因 常染色体显性遗传 突变 

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