一青少年型开角型青光眼家系的分子遗传学研究  

A molecular genetical research of a juvenile open-angle glaucoma pedigree

作　　者：龙巧燕 何芬 马蕾 李丹丽 王希振 廖海兰 刘旭阳 Long Qiaoyan;He Fen;Ma Lei;Li Danli;Wang Xizhen;Liao Hailan;Liu Xuyang(Department of Ophthalmology,Shenzhen Longgang People's Hospital,Shenzhen 518116,China;Shenzhen Eye Hospital,Shenzhen 518000,China;Xiamen Ophthalmology Center Affiliated to Xiamen University,Guangdong 361000,China)

机构地区：[1]深圳市龙岗人民医院眼科,518116 [2]深圳市眼科医院 [3]厦门大学附属厦门眼科中心

出　　处：《临床眼科杂志》2019年第6期493-499,共7页Journal of Clinical Ophthalmology

基　　金：广东省医学科研基金(编号:A2018507);国家自然科学基金(编号:81500718)

摘　　要：目的收集一个常染色体显性遗传的青少年开角型青光眼(JOAG)家系,分析该家系的临床特征和分子遗传学特点。方法收集一个JOAG家系的临床资料,包括详细的既往病史、生长发育史、生育史等,并进行全面的眼部和全身检查,包括视功能、眼压、眼前节和眼后节检查等。采集家系患者和正常成员的外周静脉血提取基因组DNA,筛选疾病相关基因序列改变,定位致病突变后,通过生物信息学的方法准确鉴定碱基突变和结构性变异,综合考虑家系资料、测序数据和现有多态性数据,设计分析方法,对所有变异进行筛查,从而确定致病变异,并分析其与患者临床特征的关系。结果该家系呈常染色体显性遗传模式,患者表现为眼压升高,房角异常,发病年龄均低于40岁,且无其它疾病表征。分子遗传学分析上,经筛选MYOC、CYP1B1和WDR36等青光眼相关候选基因,仅发现一些单核苷酸多态性(SNP)位点。但携带有MYOC基因的SNP位点T353I的JOAG患者发病年龄早,且病情发展的更快、更重。结论该JOAG家系中发现MYOC基因的单核苷酸多态性位点T353I与JOAG易感性相关,这是中国人所特有的一种多态性序列改变,与JOAG的严重程度有关,有助于MYOC基因型与临床表型关系的研究。Objective To investigate the clinical phenotype and molecular genetic characteristics of a Chinese family with autosomal dominant inherited juvenile open-angle glaucoma(JOAG).Methods All subjects in this pedigree underwent systematic history-taking as well as systemic and ophthalmic examinations, including visual acuity, intraocular pressure, direct ophthalmoscopy and fundus examination. The diagnosis was produced based on detailed ophthalmic examination of the proband. Peripheral venous blood was collected for DNA extraction. Disease-related DNA sequence was screened to identify mutant genes. Suspicious mutations were predicted with bioinformatics analysis. All variants were verified and analyzed with phenotypes.Results The four-generation family inherited as autosomal dominant inheritance trait. All the affected subjects in this pedigree had elevated intraocular pressure, abnormal anterior chamber angle and the age of onset was typically less than 40 years without any other abnormal symptoms. After screening of glaucoma-related candidate genes, including MYOC, OPTN, CYP1 B1 and WDR36, only several single nucleotide polymorphisms were identified. Carriers of T353 I, which was a SNP of the MYOC gene, had earlier glaucoma onset and faster progression.Conclusions A single nucleotide polymorphism T353 I of MYOC gene was associated with genetic susceptibility of JOAG in this study. This SNP is a unique polymorphic sequence change in Chinese, which is related to the severity of JOAG. Our finding may contribute to further researches regarding the association between phenotype and genotype of the MYOC gene.

关 键 词：青少年开角型青光眼 分子遗传学 基因突变 

分 类 号：R73[医药卫生—肿瘤]