一个中国Avellino型角膜营养不良家系的分子遗传学分析  

Molecular genetic analysis of a Chinese Avellino corneal dystrophy family

作　　者：樊宁[1] 刘璐[1] 王芝[1] 计虹[2] 杨洁[1] 黎明[1] 蒋丽琼[1] 刘旭阳[1] 

机构地区：[1]深圳暨南大学附属深圳眼科医院深圳市眼科医院深圳市眼科学重点实验室,深圳518040 [2]襄阳爱尔眼科医院集团襄阳爱尔眼科医院计虹,襄阳441000

出　　处：《中华实验眼科杂志》2014年第8期718-722,共5页Chinese Journal Of Experimental Ophthalmology

基　　金：国家自然科学基金项目（81200688、81270995、81170851、81371009）

摘　　要：背景研究发现，转化生长因子B诱导（TGFflI）基因是角膜营养不良最常见的致病基因，但rG印，基因突变与患者表型的关系研究目前仍然很少。目的探讨一个中国汉族Avellino角膜营养不良（ACD）家系的临床特征及致病原因，分析TGFfll基因突变与患者表型的关系。方法收集一个中国汉族ACD家系共3代19名家系成员，对现存活的5例患者和13名表型正常成员进行研究，采用裂隙灯显微镜、眼前节OCT、激光扫描共焦显微镜等检查方法观察受检者角膜病变的临床特点。收集所有受检者外周静脉血各2ml，对rG邛，基因进行突变分析和DNA测序。结果先证者诊断为ACD，该家系共6例患者，已去世1例，3代家系中每代均有患病者，男女患病概率相等，遗传模式符合常染色体显性遗传。该家系中3例女性患者角膜混浊病灶的形态呈面包屑样、条索样和点片状，而2例男性患者角膜混浊呈点状；女性患者角膜病变范围大于男性患者；家系中女性患者的视力为0．4～0．9，男性患者视力均为1．0。女性患者和男性患者激光扫描共焦显微镜下和眼前节OCT检查结果均无明显差别。所有患者rG邛，基因中发现第4外显子的C．372G〉A（P．R124H）杂合突变（碱基G〉A），导致第124位的精氨酸变成组氨酸，并发现TGFflI基因8号和12号外显子两个位点存在同义单核苷酸多态性（SNP）（C．981G〉A，V327V和e．1626T〉C，F542F），而家系中表型正常成员未发现此类改变。结论阳邛，基因的R124H突变为该ACD家系的致病突变，该家系中女性患者表型重于男性患者，未发现其与DNA测序结果相关。Background Previous studies demonstrated that the transforming growth factor beta induced （ TGF[31 ） gene is the most common disease-causing gene for corneal dystrophy. However,if DNA variant is associated with pbenotype is unclear. Objective This study was to identify the clinical features and molecular genetics of a Chinese family with Avellino corneal dystrophy （ACD） and analyze the association between TGFfll mutation and phenotype. Methods This study complied with Helsinki Declaration and was approved by Ethic Commission of Shenzhen Eye Hospital. Informed consent was obtained from each individual prior to any medical examination. A Chinese ACD family was collected with 19 members of 3 generations. The corneas were clinically examined by slit lamp microscope, ocular anterior segment opitical coherence tomography （OCT） and laser scanning confocal microscope in 5 affected members and 13 unaffected subjects. The peripheral blood sample of 2 ml was collected for the TGF^I mutation analysis （ 17 exons） and DNA sequencing. Results The proband was diagnosed as ACD. Total 6 patients were found in the pedigree,and 1 male patient dead. This family accorded with an autosomal dominant in heritance pattern. The morphology of corneal opacification showed the bread crumbs-like,stripes-like and patchy-like, and that of male patients was dots-like. The lesion size was larger in female patients than that in male patients. Thevisual acuity was 0.4-0.9 in female patients and 1.0 in male patients. The findings of OCT and laser scanning confoeal microscope were similar between the female and male patients. Sequencing of TGFBI gene revealed a heternzygous transition （ c. 372 G〉A） in exon 4,which resulted in Arg124His （R124H） being co-segregated with the disease in affected family members, but not in the unaffected members. The single nucleotide polymorphism （SNP） also was seen in exon 8 and 12 （e. 981G〉A, V327V and c. 1626T〉C,F542F） in affected members. No these variants were detected in the una

关 键 词：遗传性角膜营养不良 转化生长因子B 遗传基因学 遗传易感性 DNA突变分析 基因型 表型 家系 

分 类 号：R772.21[医药卫生—眼科]