FRMD7基因新突变位点导致先天性眼球震颤一家系  

A novel mutation of FRMD7 in a Chinese family with X-linked congenital nystagmus.

作　　者：周晨晨 蒋沁[1] 李秀苗[1] 王成虎[1] Zhou Chen-chen;Jiang Qin;Li Xiu-miao(The Affiliated Eye Hospital of Nanjing Medical University,Nanjing 210000,China.)

机构地区：[1]南京医科大学附属眼科医院,210000

出　　处：《中国斜视与小儿眼科杂志》2021年第2期25-26,I0001,I0002,共4页Chinese Journal of Strabismus & Pediatric Ophthalmology

基　　金：南京医科大学科技发展基金(编号:2017NJMUZD128)。

摘　　要：目的对一先天性眼球震颤家系进行致病基因筛查和遗传分析.方法对该家系中参与研究的10名成员进行全面的眼科及系统检查,并采集外周静脉血,对先证者进行已知的814个遗传性眼病相关候选基因进行定点捕获测序分析,筛选出候选致病基因位点,再在家系成员中进行共分离验证.结果该家系所有患者均有不同程度的眼球水平震颤,部分患者伴有代偿头位、不同程度的中心视力下降等.家系符合X连锁显性遗传特征,通过测序、生物学分析及验证,发现该家系内患者FRMD7(FERM domain containing 7)基因的剪切位点发生突变[c.741+2T>C],经Human Splicing Finder 3.1软件预测提示该突变破坏了FRMD7基因的剪接供体位点,可能会导致FRMD7基因的mRNA发生改变,从而产生新的氨基酸序列,使编码蛋白的结构和功能受到了破坏.结论FRMD7基因剪切位点突变[c.741+2T>C]为本研究中先天性眼球震颤家系的致病突变位点,该位点为一新发突变位点,本研究扩大了FRMD7基因的突变频谱.Objective To screen and analyze pathogenic gene mutation in a Chinese family with X-linked congenital nystagmus.Methods Comprehensive ophthalmological and physical examinations was performed on 10 members from the family with congenital nystagmus.Targeted gene capture sequencing analysis which containing 814 candidate genes related to ophthalmic disorders was performed on proband.Candidate pathogenic gene were selected through bioinformatic analysis,and Sanger sequencing were performed on the other family members to verify the candidate disease-causing mutation.Results All patients in this family have different levels of horizontal nystagmus,and some patients have compensatory head posture and central vision loss.The pedigree accords with dominant X chromosome inheritance characteristics.All patients with congenital nystagmus in the family harbored a novel splice site mutation(c.741+2 T>C).This mutation is predicted as pathogenetic by the Human Splicing Finder 3.1 software,which can affect the protein structure and function by disrupt splice donor site of wild-type FRMD7.Conclusions Our study identified a novel mutation of FRMD7(c.741+2 T>C) responsible for congenital nystagmus in a Chinese family,which enhances the spectrum of variants in the FEMD7 of X-linked Congenital nystagmus.

关 键 词：先天性眼球震颤 FRMD7基因 基因测序 剪切位点突变 

分 类 号：R777.46[医药卫生—眼科]