中国汉族Cohen综合征一家系VPS13B基因变异及临床表型分析  

VPS13B gene variation and clinical phenotype of Cohen syndrome in a Chinese Han family

作　　者：李瑞敏 郭庆歌 李亚 游雅 雷博 Li Ruimin;Guo Qingge;Li Ya;You Ya;Lei Bo(Xinxiang Medical University Graduate School,Xinxiang 453003,China;Department of Ophthalmology,Henan Provincial People's Hospital,Henan Eye Hospital,Zhengzhou 450003,China)

机构地区：[1]新乡医学院研究生院,新乡453003 [2]河南省人民医院眼科河南省立眼科医院,郑州450003

出　　处：《中华实验眼科杂志》2023年第9期871-878,共8页Chinese Journal Of Experimental Ophthalmology

基　　金：国家自然科学基金项目(82071008、82271084);国家重点研发计划项目(2020YFC2008204)。

摘　　要：目的分析VPS13B基因复合杂合变异导致的Cohen综合征患者的致病性以及临床特征。方法采用家系调查研究,收集2021年9月于河南省立眼科医院就诊的中国汉族Cohen综合征一家系共2代3人,其中患者1例。收集先证者及其父母的临床资料,完善相关眼科及全身检查以评估临床表型;采集该家系成员外周静脉血样本,提取全基因组DNA,进行全外显子组测序。对家系成员中进行Sanger测序和家系共分离分析。根据ACMG指南对筛选出来的变异位点进行致病性评分;应用在线工具对变异位点进行致病性预测。以"Cohen综合征"、"Cohen syndrome"和"VPS13B基因"为关键词,检索在线人类孟德尔遗传数据库、PubMed数据库、中国知网、万方数据知识服务平台以及维普中文科技期刊数据库中Cohen综合征相关文献。总结文献中不同患者的临床表现以及致病位点,分析基因型和临床表型的关系。结果该家系符合常染色体隐性遗传。先证者,男,5岁,双眼夜盲伴畏光、上睑下垂、下睑内翻、倒睫,双眼高度近视,周边视网膜骨细胞样色素沉积,周边部视网膜外层萎缩变薄,闪光视网膜电图未检测出波形;全身发育迟缓,典型面部特征,手指脚趾细长,扁平足,足内翻,肌张力减退,未发现心脏异常;性格过度开朗。先证者临床表现符合Cohen综合征。先证者父母临床表型及辅助检查结果均未见明显异常。全外显子测序显示,先证者携带VPS13B基因1个无义变异c.11713C>T(p.Gln3905*)和1个剪接变异c.6940+1G>T。经Sanger测序验证,上述变异在该家系中呈共分离。其中c.11713C>T(p.Gln3905*)为未报道的新变异位点,该变异位点使其编码的蛋白质提前终止,影响蛋白质的正常功能。ACMG指南显示2种变异均为致病变异。共检索到12篇中国Cohen综合征的变异位点及临床特征相关文献,结合本研究结果共发现中国患者人群中VPS13B变异位点共24个,其中移�Objective To analyze the pathogenicity and clinical characteristics of patients with Cohen syndrome caused by a compound heterozygous variation of VPS13B gene.Methods A pedigree investigation was conducted.A Chinese Han family with Cohen syndrome was recruited from Henan Eye Hospital in September 2021.There were three members of two generations in this family,including one patient.The clinical data of the proband and his parents were collected,and the relevant ophthalmic and general examinations were performed to evaluate the clinical phenotype.The peripheral venous blood samples of the family members were collected to extract whole genomic DNA,and the whole exome sequencing was performed.Sanger sequencing and pedigree co-segregation analysis were performed among the family members.According to the ACMG guidelines,the pathogenicity of the selected variants was evaluated and the online tools were used to predict the pathogenicity of the variants.Relevant literature of Cohen syndrome were retrieved in Online Mendelian Inheritance in Man(OMIM)and PubMed,China National Knowledge Infrastructure and Wanfang databases by taking Cohen syndrome and VPS13B gene as the searching keywords.The clinical manifestations and pathogenic variants of patients in the literature were summarized,and the relationship between genotype and clinical phenotype was analyzed.This study protocol adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Henan Eye Hospital(No.HNEECKY-2019[15]).Both the subject and the patient's guardian were aware of the study purpose and method.Written informed consent was obtained.Results The family was consistent with autosomal recessive inheritance.The proband,a 5-year-old male,had bilateral night blindness with photophobia,ptosis,lower eyelid entropion,and trichiasis;high myopia in both eyes;osteoblastoid pigmentation in the peripheral retina,atrophy and thinning of the outer layer of the peripheral retina,extinguished flashing electroretinogram;global growth retardation,typical fac

关 键 词：Cohen综合征 VPS13B 基因变异 视网膜色素变性 表型 

分 类 号：R596[医药卫生—内科学]