摘要
目的确定1个Schubert-Bornschein型不完全型先天性静止性夜盲(CSNB)家系的致病基因突变。方法回顾性临床研究。2021年2月于河南省人民医院经临床、基因检查确诊的一个汉族Schubert-Bornschein型不完全型CSNB家系中1例患者及其父母、兄长纳入研究。详细询问患者病史、家族史并行最佳矫正视力(BCVA)、色觉、眼底彩色照相、全视野视网膜电图(ERG)、频域光相干断层扫描(OCT)检查。采集受试者外周静脉血5 ml,提取全基因组DNA。受检者基因组DNA进行文库构建、聚合全外显子探针进行捕获。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(Ⅱ2)双眼BCVA均为0.4;色觉检查不能辨认红色。眼底检查未见明显异常。双眼黄斑区视网膜厚度轻度变薄。全视野ERG检查,双眼暗适应3.0刺激下ERG b波振幅明显降低,呈负波形。先证者母亲(Ⅰ2)双眼BCVA、色觉、眼底彩色照相、频域OCT检查均正常。全视野ERG检查,双眼各反应振幅轻度降低,暗适应震荡电位振幅明显降低。基因检测结果显示,先证者(Ⅱ2)电压依赖钙离子通道α1F亚基基因(CACNA1F基因)第14号外显子存在c.1761dupC半合子突变。蛋白序列同源性分析结果显示,该位点在多个物种中均高度保守;生物信息学分析结果显示,CACNA1F基因c.1761dupC(pY588fs)其后发生移码突变,在第10位变成终止密码子在蛋白质保守区出现翻译终止。根据美国医学遗传学和基因组学学会标准和指南,该突变判断为可能致病性变异。先证者母亲(Ⅰ2)为该位点突变携带者。先证者父亲、兄长临床及基因检测结果均未见异常。结论CACNA1F基因c.1761dupC是该Schubert-Bornschein型不完全型CSNB家系致病的突变位点。
Objective To determine the pathogenic gene mutation in a family with incomplete congenital quiescent night blindness(CSNB)of Schubert-Bornschein type.Methods A retrospective clinical study.In February 2021,one patient and his parents and elder brother from a Han Chinese incomplete CSNB of Schubert-Bornschein type family diagnosed by clinical and genetic examination at Henan Provincial People's Hospital were included in the study.The patient’s medical history,family history were inquired;best corrected visual acuity(BCVA),color vision,fundus color photography,full-field electroretinogram(ERG),and frequency domain optical coherence tomography(OCT)were examined in detail.Five ml of the subject’s peripheral venous blood was collected and the whole genome DNA was extracted.The genomic DNA of the subject was library constructed,and all-exon probes were polymerized for capture.The suspected pathogenic mutation site was verified by Sanger,and the pathogenicity of the gene mutation site was determined by parallel bioinformatics analysis.Results The BCVA of both eyes of the proband(Ⅱ2)was 0.4;the color vision test could not recognize the red color.Fundus examination showed no obvious abnormalities.The retina thickness in the macular area of both eyes was slightly thinned.ERG examination of the whole field showed that the amplitude of ERG b wave was significantly reduced under the stimulation of binocular dark adaptation 3.0 and showed a negative waveform.The mother of the proband(Ⅰ2)had normal BCVA,color vision,fundus color photography,and frequency domain OCT examination.The full-field ERG examination showed that the amplitude of each eye reaction was slightly reduced,and the amplitude of the dark adaptation shock potential was significantly reduced.Genetic testing showed that the proband(Ⅱ2)had a c.1761dupC hemizygous mutation in exon 14 of the voltage-dependent calcium channelα1F subunit gene(CACNA1F gene).The results of protein sequence homology analysis showed that the site was highly conserved in multiple
作者
李冠峰
周钟强
唐贺
魏圆梦
彭海鹰
史平玲
梁迎娟
孙先桃
卢跃兵
Li Guanfeng;Zhou Zhongqiang;Tang He;Wei Yuanmeng;Peng Haiying;Shi Pingling;Liang Yingjuan;Sun Xiantao;Lu Yuebing(Department of Opthalmology,Henan Children's Hospital,Children's Hospital Affiliated of Zhengzhou University,Henan Provincial Key Laboratory of Children's Genetic and Metabolic Diseases,Zhengzhou 450018,China;Henan Eye Institute,Henan Eye Hospital,People's Hospital of Zhengzhou University,Henan Provincial People's Hospital,Zhengzhou 450003,China)
出处
《中华眼底病杂志》
CAS
CSCD
北大核心
2021年第11期860-864,共5页
Chinese Journal of Ocular Fundus Diseases
