后节小眼畸形-视网膜色素变性一家系致病基因突变检测  

Gene mutation detection of the posterior microphthalmia-retinal pigment degeneration family

作　　者：李杰 高韶晖 邢亚斯 路小楠 戴淑真 Li Jie;Gao Shaohui;Xing Yasi;Lu Xiaonan;Dai Shuzhen(Department of Ophthalmology,Henan Provincial People's Hospital,People's Hospital of Zhengzhou University,Henan Eye Hospital,Henan Eye Institute,Henan Key Laboratory of Ophthalmology and Visual Science,Zhengzhou 450003,China)

机构地区：[1]河南省人民医院眼科郑州大学人民医院眼科河南省立眼科医院河南省眼科研究所河南省眼科学与视觉科学重点实验室,450003

出　　处：《中华眼底病杂志》2021年第11期848-853,共6页Chinese Journal of Ocular Fundus Diseases

基　　金：河南省医学科技攻关计划(联合共建)项目(LHGJ20200069)。

摘　　要：目的确定后节小眼畸形-视网膜色素变性一家系的致病基因。方法回顾性临床研究。2019年7月于河南省立眼科医院经临床及基因检查确诊的后节小眼畸形-视网膜色素变性一家系1例患儿(先证者)和3名家系成员纳入研究。采集其病史及家族史,绘制家系图谱;并行视力、视野、眼底彩色照相、光相干断层扫描、视网膜电图(ERG)检查。采集先证者及其父母、妹妹的外周静脉血,提取全基因组DNA。应用全外显子测序技术进行全外显子测序,检测基因突变位点。对可疑致病突变位点通过Sanger进行验证,并行生物信息学分析确定基因突变位点的致病性。结果先证者10月龄时父母发现其视力差。至3岁时右眼、左眼矫正视力分别为0.3、0.4。眼前节未见异常。双眼极高度远视。眼轴长度分别为14.47、15.78 mm。双眼视盘偏小、潮红;黄斑区可见皱襞,未见明显色素紊乱。ERG检查,双眼视杆细胞反应、最大混合反应轻-中度降低,单闪视锥反应、30 Hz闪烁反应中-重度降低。全外显子测序结果显示,先证者膜型卷曲相关蛋白(MFRP)基因第4、13外显子上分别存在c.363delC/p.Thr121Thrfs*16、c.1627C>T/p.Gln543Stop,37的复合杂合突变。前者为移码突变,编码16个氨基酸后终止;后者为无义突变,截断了37个氨基酸。两者均属于基因功能失活突变。生物信息学分析提示高致病性,并符合家系共分离。先证者母亲、妹妹携带c.363delC,父亲携带c.1627C>T。结论MFRP基因c.363delC/p.Thr121Thrfs*16、c.1627C>T/p.Gln543Stop,37复合杂合突变可能是本家系的致病基因。Objective To identify the causative genes of the posterior microphthalmia-retinal pigment degeneration family.Methods A retrospective clinical study.One child(proband)and 3 family members of a family with posterior microphthalmia-retinitis pigmentosa diagnosed by clinical and genetic examination at Henan Provincial People's Hospital in July 2019 were included in the study.Medical history and family history,and draw pedigree of the patients was collected.Visual acuity,visual field,fundus color photography,optical coherence tomography and electroretinogram(ERG)were examined.The peripheral venous blood of the proband,his parents and sister,and extract the whole genome DNA was collected.Whole-exome sequencing was used to detect genetic variations,the suspected pathogenic variations were verified by Sanger sequencing,and the pathogenicity was determined by bioinformatics analysis.Results The parents discovered the proband was poor vision at the age of 10 months.At the age of 3,the best corrected visual acuity of the right eye and the left eye were 0.3 and 0.4,respectively.No abnormality was found in anterior segment.Extremely high hyperopia in both eyes.The axial length was 14.47 mm and 15.78 mm,respectively.The optic disc of both eyes was relatively small and flushed,retinal folds can be observed in macular area,and no obvious pigment deposition was found.ERG examination showed that the rod system response and the maximal combined response of both eyes decreased slightly to moderately,and the single-flash cone response and the 30 Hz flicker response decreased moderately to severely.Genetic analysis revealed two novel mutations in the membrane frizzled-related protein(MFRP)gene in the proband:c.363delC/p.Thr121Thrfs*16,c.1627C>T/p.Gln543Stop,37 in exon 4 and 13,the former was a frameshift mutation,encoding 16 amino acids and then terminated,and the latter was an nonsense mutation,truncated 37 amino acids,both which were predicted to be pathogenic and segregate with disease.The mother and sister carried c.363delC,and t

关 键 词：小眼 色素性视网膜炎 MFRP基因突变 

分 类 号：R77[医药卫生—眼科]