Retinitis pigmentosa(RP),a major cause of inherited blindness worldwide,is highly heterogeneous.This study aimed to identify mutations in a Chinese cohort of sporadic probands with presumptive RP.Whole exome sequencin...Retinitis pigmentosa(RP),a major cause of inherited blindness worldwide,is highly heterogeneous.This study aimed to identify mutations in a Chinese cohort of sporadic probands with presumptive RP.Whole exome sequencing represents a considerable advancement in the identification of mutations associated with Mendelian diseases,such as RP.In this study,whole exome sequencing analysis was performed in a Chinese cohort of 95 sporadic probands who were initially diagnosed with RP,in order to identify disease mutations.All detected variations were confirmed by direct Sanger sequencing,and potential pathogenicity was assessed by predictions of the mutations’functions.The overall mutation rate of presumptive RP genes for this cohort was 30.5%(n=29 of 95 probands).Forty-four mutations were identified in 19 RP genes,among which 40 mutations were novel.Eleven probands carried mutations in autosomal dominant genes(38.0%),16 probands carried mutations in autosomal recessive genes(55.2%),and 2 probands carried mutations in X-linked genes(6.9%).Twenty-eight mutations in 18 genes linked to other retinal diseases in 23 probands were also identified.Overall,mutations were detected in 52 probands(54.7%).The recurrent and novel mutations reported here will expand potential understanding of the pathogenesis of RP and other retinal diseases.展开更多
分析X-连锁腓骨肌萎缩症1型(X-linked Charcot-Marie-Tooth disease type 1,CMT1X)一家系的临床表现、电生理与突变基因特点。该家系为两代4人,共有2例CMT1X患者。先证者12岁起病,先证者母亲40岁起病,两者均表现为进行性肢体无力、萎缩...分析X-连锁腓骨肌萎缩症1型(X-linked Charcot-Marie-Tooth disease type 1,CMT1X)一家系的临床表现、电生理与突变基因特点。该家系为两代4人,共有2例CMT1X患者。先证者12岁起病,先证者母亲40岁起病,两者均表现为进行性肢体无力、萎缩,行走不稳。神经电生理检查均提示:四肢多发感觉运动神经损害(轴索损害为主并脱髓鞘);多发肌肉呈神经源性损害。突变基因分析,先证者存在缝隙连接蛋白B1(gap junction protein Bata-1,GJB1)基因c.283 G>T(p.V95L)半合子突变,先证者母亲存在GJB1基因c.283 G>T(p.V95L),杂合突变。CMT1X是第二常见的腓骨肌萎缩症(Charcot-Marie-Tooth disease,CMT)类型,由GJB1基因突变引起,临床表现为进行性发展的周围神经病可合并中枢神经系统损害,基因检测有助诊断。展开更多
ObjectiveTo seek potential pathogenic variants in sarcomere genes in arrhythmogenic cardiomyopathy(ACM)and describe the characteristics.Methods and Results We performed targeted sequencing of 14sarcomere genes in 118 ...ObjectiveTo seek potential pathogenic variants in sarcomere genes in arrhythmogenic cardiomyopathy(ACM)and describe the characteristics.Methods and Results We performed targeted sequencing of 14sarcomere genes in 118 cases with the clinical diagnosis of ARVC and Sanger sequencing of the specific variants in family members of the probands.展开更多
基金This study was supported by the National Key Scientific Research Program(No.2016YFC0905200,toZY)the National Natural Science Foundation of China(No.81170883,81790643 and 81430008(to ZY),81300802 and 81670895(to LH),81271048(to JY),81570848 and 81100693(to CQ))+1 种基金by the Department of Science and Technology of Sichuan Province,China(No.2014SZ0169,2015SZ0052(to ZY),2015JQO057(to LH),2016HH0072(to LH),2017JQ0024(to LH),2015SZ0060(to YL),2013JY0195(to LH),2015SZ0060(to YL),2014FZ0124(to DYL)and 2015JZ0004(to CQ))High-level Talents Program of UESTC Y03001023601021016(to LH).
文摘Retinitis pigmentosa(RP),a major cause of inherited blindness worldwide,is highly heterogeneous.This study aimed to identify mutations in a Chinese cohort of sporadic probands with presumptive RP.Whole exome sequencing represents a considerable advancement in the identification of mutations associated with Mendelian diseases,such as RP.In this study,whole exome sequencing analysis was performed in a Chinese cohort of 95 sporadic probands who were initially diagnosed with RP,in order to identify disease mutations.All detected variations were confirmed by direct Sanger sequencing,and potential pathogenicity was assessed by predictions of the mutations’functions.The overall mutation rate of presumptive RP genes for this cohort was 30.5%(n=29 of 95 probands).Forty-four mutations were identified in 19 RP genes,among which 40 mutations were novel.Eleven probands carried mutations in autosomal dominant genes(38.0%),16 probands carried mutations in autosomal recessive genes(55.2%),and 2 probands carried mutations in X-linked genes(6.9%).Twenty-eight mutations in 18 genes linked to other retinal diseases in 23 probands were also identified.Overall,mutations were detected in 52 probands(54.7%).The recurrent and novel mutations reported here will expand potential understanding of the pathogenesis of RP and other retinal diseases.
文摘ObjectiveTo seek potential pathogenic variants in sarcomere genes in arrhythmogenic cardiomyopathy(ACM)and describe the characteristics.Methods and Results We performed targeted sequencing of 14sarcomere genes in 118 cases with the clinical diagnosis of ARVC and Sanger sequencing of the specific variants in family members of the probands.
