早发性严重视网膜营养不良一家系TULP1和CNGB1基因突变

目的:确定早发性严重视网膜营养不良（EOSRD）一家系的致病基因突变。方法:回顾性临床研究。2018年8月于河南省立眼科医院检查确诊的一个汉族EOSRD家系中1例患者及3名家系成员纳入研究。详细采集患者病史后，对受试者行最佳矫正视力（BCVA ）、裂隙灯显微镜联合前置镜、眼底彩色照相、频域光相干断层扫描（SD-OCT）...

Novel mutations in the TULP1 and CNGB1 genes in a family affected with early onset severe retinal dystrophy

Objective To identify the pathogenic gene mutations in a family with early onset severe retinal dystrophy(EOSRD).Methods A retrospective clinical study.One patient and three family members from a Han of EOSRD who were diagnosed at Henan Eye Hospital in August 2018 were included in the study.After the detailed history of the patients was collected,all participants underwent best corrected visual acuity(BCVA),slit-lamp,fundus biomicroscopy with the slit lamp,untra-widefield fundus color photography,spectral-domain optical coherence tomography(SD-OCT)and full-field electroretinography(ff-ERG).The subject's peripheral venous blood of 5 ml was collected and the whole genome DNA was extracted.A genetic eye disease capture chip containing 441 disease-causing genes was used for targeted capture and enrichment of high-throughput sequencing,and Sanger sequencing was performed for the clear pathogenic mutation sites;the analysis software was used for bioinformatics analysis of the mutation sites.Results A 6-year-old female proband developed poor night vision in both eyes after 1 year old.The BCVA of both eyes were 0.1.The color of the optic disc was slightly lighter;the diameter of the retinal vessels was slightly reduced,and extensive pigment changes can be seen in the retina outside the vascular arch.SD-OCT examination showed that the outer membrane,ellipsoid zone and chimera zone in the central fovea of both eyes were unclear and intermittent.The visual area outside the fovea was neuroepithelial outer plexiform layer,outer nuclear layer,outer membrane,ellipsoid zone.The chimera zone gradually disappeared,and the thickness of the pigment epithelial layer was not uniform.In ff-ERG examination,the functions of the binocular cone and rod system were severely decreased.The results of genetic testing showed that there were c.921C>A homozygous mutations in the Tubby-like protein(TULP1)gene of the proband,and c.3121C>T and c.3488G>A compound heterozygous mutations in the cyclic nucleotide gated channel beta 1(CNGB1)gene.Amino acid conservation analysis results showed that the above three mutation sites were highly conserved in multiple species;bioinformatics analysis results showed that TULP1 gene c.921C>A(p.Cys307^*)had translation termination in the protein conserved region,CNGB1 gene c.3121C>T(p.Argl041Trp)and c.3488G>A(p.Glyl 163Glu)had amino acid polarity changes in the protein conserved region,which led to major changes in the protein spatial structure.Conclusion TULP1 gene c.921C>A homozygous mutation,CNGB1 gene c.3121C>T and c.3488G>A compound heterozygous mutation are the mutation sites of this EOSRD family.