Yang Yin, Yang Yeming, Huang Lulin, Zhai Yaru, Li Jie, Jiang Zhilin, Gong Bo, Fang Hao, Kim Ramasamy, Yang Zhenglin, Sundaresan Periasamy, Zhu Xianjun, Zhou Yu
Sichuan Provincial Key Laboratory for Human Disease Gene Study, School of Medicine, Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Department of Ophthalmology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.
Sci Rep. 2016 Sep 27;6:33681. doi: 10.1038/srep33681.
Retinitis pigmentosa (RP) is a leading cause of inherited blindness characterized by progressive degeneration of the retinal photoreceptor cells. This study aims to identify genetic mutations in a Chinese family RP-2236, an Indian family RP-IC-90 and 100 sporadic Indian individuals with autosomal recessive RP (arRP). Whole exome sequencing was performed on the index patients of RP-2236, RP-IC-90 and all of the 100 sporadic Indian patients. Direct Sanger sequencing was used to validate the mutations identified. Four novel mutations and one reported mutation in the crumbs homolog 1 (CRB1) gene, which has been known to cause severe retinal dystrophies, were identified. A novel homozygous splicing mutation c.2129-1G>C was found in the three patients In family RP-2236. A homozygous point mutation p.R664C was found in RP-IC-90. A novel homozygous mutation p.G1310C was identified in patient I-44, while novel compound heterozygous mutations p.N629D and p.A593T were found in patient I-7. All mutations described above were not present in the 1000 normal controls. In conclusion, we identified four novel mutations in CRB1 in a cohort of RP patients from the Chinese and Indian populations. Our data enlarges the CRB1 mutation spectrums and may provide new target loci for RP diagnose and treatment.
视网膜色素变性(RP)是遗传性失明的主要原因,其特征是视网膜光感受器细胞进行性退化。本研究旨在鉴定一个中国RP-2236家系、一个印度RP-IC-90家系以及100名散发的常染色体隐性RP(arRP)印度个体中的基因突变。对RP-2236、RP-IC-90的先证者以及所有100名散发的印度患者进行了全外显子组测序。采用直接桑格测序法验证所鉴定的突变。在已知会导致严重视网膜营养不良的crumbs同源物1(CRB1)基因中鉴定出四个新突变和一个已报道的突变。在RP-2236家系的三名患者中发现了一个新的纯合剪接突变c.2129-1G>C。在RP-IC-90中发现了一个纯合点突变p.R664C。在患者I-44中鉴定出一个新的纯合突变p.G1310C,而在患者I-7中发现了新的复合杂合突变p.N629D和p.A593T。上述所有突变在1000名正常对照中均未出现。总之,我们在中国和印度人群的RP患者队列中鉴定出CRB1基因的四个新突变。我们的数据扩大了CRB1突变谱,可能为RP的诊断和治疗提供新的靶点。