角膜营养不良患者TGFBI基因突变特点及基因型-表型关系  

Gene mutation and genotype-phenotype description in corneal dystrophy associated with TGFBI genes

作　　者：许可[1] 孙旭光[1] 谢玥[1] 梁庆丰[1] 张晓慧[1] 蒋凤[1] 李杨[1] 

机构地区：[1]首都医科大学附属北京同仁医院北京同仁眼科中心北京市眼科研究所北京市眼科学与视觉科学重点实验室,100005

出　　处：《中华眼视光学与视觉科学杂志》2016年第3期153-159,共7页Chinese Journal Of Optometry Ophthalmology And Visual Science

摘　　要：目的分析TGFBI基因相关角膜营养不良患者的基因突变特点及基因型-表型关系。方法系列病例研究。应用聚合酶链式反应（PCR）技术对63例角膜营养不良患者基因组DNA进行TGFBI基因扩增并直接测序，所有患者进行详细的眼科检查，包括最佳矫正视力（BCVA）、眼前节检查，部分患者行角膜激光共聚焦显微镜（HRT）检查。结果63例患者中有48例检测到9种TGFBI基因杂合错义突变，包括8种已报道过的致病突变[c．371G〉A（p．R124H）、c．370C〉T（p．R124C）、c．371G〉T（p．R124L）、c．1663C〉T（p．R555W）、c．1664G〉A（p．R555Q）、C．1514T〉A（p．V505D）、c．1859C〉A（p．A620D）、C．1877A〉G（p．H626R）]和1种新突变[c．1694T〉A（p．L565H）]，突变主要分布于第4号外显子，突变频次为37次，其中携带c．371G〉A（p．R124H）突变的Avellino角膜营养不良患者所占比例最大（28／48）。48例阳性患者平均发病年龄为（31．3±16．8）岁，裂隙灯显微镜检查患者双眼可见角膜上皮至基质层均混浊，不同突变导致患者角膜沉积物形态各异。结论本研究新发现的c．1694T〉A（P．L565H）突变，拓展了角膜营养不良TGFBI基因突变谱。并再次证实371G〉A（p．R124H）是亚洲TGFBI基因突变相关角膜营养不良最常见的突变形式。角膜营养不良患者存在表型异质性，角膜沉积物特征与其携带的基因突变明显相关，以分子遗传学为基础的角膜营养不良分类方法可以提高临床诊断的准确性。Objective To investigate the TGFBI gene mutations of patients with corneal dystrophy and describe their phenotype specificity. Methods In a case series study, TGFBI genes were amplified by a polymerase chain reaction and directly sequenced for 63 patients. Each proband underwent clinical examination, including best-corrected visual acuity （BCVA） using E decimal charts, slit-lamp biomicroscopy, and confoeal microscopy in some patients. Results Nine TGFBI gene heterozygosis missense mutations were found in 48 patients, including 8 reported pathogenic mutations： c.371G〉A（p.R124H）, c.370C〉T（p.R124C）, c.371G〉T（p.R124L）, c.1663C〉T（p.R555W）, c.1664G〉A （p.R555Q）, c.1514T〉A（p.V505D）, e.1859C〉A（p.A620D）, c.1877A〉G（p.H626R） and one novel mutation： e.1694T〉A（p.L565H）. TGFBI gene mutations were most commonly located in exon 4 in 37 patients. The maximum proportion of the c.371G〉A（p.R124H） mutation was in 28 cases with Avellino. The mean age of onset was 31.3±16.8 years （range 2-61 years）. Slit-lamp biomicroscopy of 48 corneal dystrophies revealed bilateral opacity distributed in the corneal epithelium and stroma, expressing characteristic deposits. Conclusion Our findings expand the spectrum of TGFBI mutation, c.371G〉A（p.R124H） is the most common form of mutation in Asian patients with corneal dystrophy. Different forms of mutations cause characteristic deposits. Based on the molecular genetics of corneal dystrophy, classification can improve the rate of clinical diagnosis.

关 键 词：角膜营养不良 遗传性 表型 TGFBI基因 基因突变 

分 类 号：R772.2[医药卫生—眼科]