Huang Li, Xiao Xueshan, Li Shiqiang, Jia Xiaoyun, Wang Panfeng, Sun Wenmin, Xu Yan, Xin Wei, Guo Xiangming, Zhang Qingjiong
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
Exp Eye Res. 2016 May;146:252-258. doi: 10.1016/j.exer.2016.03.015. Epub 2016 Mar 16.
Cone-rod dystrophy (CORD) is a common form of inherited retinal degeneration. Previously, we have conducted serial mutational analysis in probands with CORD either by Sanger sequencing or whole exome sequencing (WES). In the current study, variants in all genes from RetNet were selected from the whole exome sequencing data of 108 CORD probands (including 61 probands reported here for the first time) and were analyzed by multistep bioinformatics analysis, followed by Sanger sequencing and segregation validation. Data from the previous studies and new data from this study (163 probands in total) were summarized to provide an overview of the molecular genetics of CORD. The following potentially pathogenic mutations were identified in 93 of the 163 (57.1%) probands: CNGA3 (32.5%), ABCA4 (3.8%), ALMS1 (3.1%), GUCY2D (3.1%), CACNA1F (2.5%), CRX (1.8%), PDE6C (1.8%), CNGB3 (1.8%), GUCA1A (1.2%), UNC119 (0.6%), RPGRIP1 (1.2%), RDH12 (0.6%), KCNV2 (0.6%), C21orf2 (0.6%), CEP290 (0.6%), USH2A (0.6%) and SNRNP200 (0.6%). The 17 genes with mutations included 12 known CORD genes and five genes (ALMS1, RDH12, CEP290, USH2A, and SNRNP200) associated with other forms of retinal degeneration. Mutations in CNGA3 is most common in this cohort. This is a systematic molecular genetic analysis of Chinese patients with CORD.
圆锥-杆营养不良(CORD)是一种常见的遗传性视网膜变性形式。此前,我们通过桑格测序或全外显子组测序(WES)对CORD先证者进行了系列突变分析。在本研究中,从108例CORD先证者(包括61例首次在此报道的先证者)的全外显子组测序数据中选取RetNet中所有基因的变异,并通过多步骤生物信息学分析进行分析,随后进行桑格测序和分离验证。汇总先前研究的数据和本研究的新数据(共163例先证者),以概述CORD的分子遗传学。在163例(57.1%)先证者中的93例中鉴定出以下潜在致病突变:CNGA3(32.5%)、ABCA4(3.8%)、ALMS1(3.1%)、GUCY2D(3.1%)、CACNA1F(2.5%)、CRX(1.8%)、PDE6C(1.8%)、CNGB3(1.8%)、GUCA1A(1.2%)、UNC119(0.6%)、RPGRIP1(1.2%)、RDH12(0.6%)、KCNV2(0.6%)、C21orf2(0.6%)、CEP290(0.6%)、USH2A(0.6%)和SNRNP200(0.6%)。发生突变的17个基因包括12个已知的CORD基因和5个与其他形式视网膜变性相关的基因(ALMS1、RDH12、CEP290、USH2A和SNRNP200)。CNGA3突变在该队列中最为常见。这是对中国CORD患者进行的系统分子遗传学分析。