Citation:Lu QK,Zhao N,Lv YS,Gong WK,Wang HY,Tong QH,Lai XM,Liu RR,Fang MY,Zhang JG,Du ZF,Zhang XN.A novel CRX mutation by whole-exome sequencing in an autosomal dominant cone-rod dystrophy pedigree.Int J Ophthalmol 2015;8(6):1112-1117,doi:10.3980/j.issn.2222-3959.2015.06.06
A novel CRX mutation by whole-exome sequencing in an autosomal dominant cone-rod dystrophy pedigree
Received:January 27, 2015  Revised:March 30, 2015
Email this Article  Add to Favorites  Print
DOI:10.3980/j.issn.2222-3959.2015.06.06
Key Words:cone-rod dystrophy; autosomal dominant cone-rod dystrophy; whole-exome sequencing; Sanger sequencing; CRX gene; mutation
Fund Project:Supported by the Zhejiang Provincial Natural Science Foundation of China (No.LY12H12001); the Ningbo Key Foundation of Society Development (No.2014C50091); the Ningbo Natural Science Foundation (No. 2012A610192); the Ningbo Yinzhou District S&T Foundation (No.YK2013-90); the Shenzhen Municipal Government of China (No.GJHZ20130417140916986).
                                   
AuthorInstitution
Qin-Kang Lu Ophthalmology Center, Yinzhou People’s Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo , Zhejiang Province, China
Na Zhao Ophthalmology Center, Yinzhou People’s Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo , Zhejiang Province, China
Ya-Su Lv Department of Cell Biology and Medical Genetics, Research Center for Molecular Medicine, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou , Zhejiang Province, China
Wei-Kun Gong Ophthalmology Center, Yinzhou People’s Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo , Zhejiang Province, China
Hui-Yun Wang Ophthalmology Center, Yinzhou People’s Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo , Zhejiang Province, China
Qi-Hu Tong Ophthalmology Center, Yinzhou People’s Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo , Zhejiang Province, China
Xiao-Ming Lai Ophthalmology Center, Yinzhou People’s Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo , Zhejiang Province, China
Rong-Rong Liu Department of Cell Biology and Medical Genetics, Research Center for Molecular Medicine, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou , Zhejiang Province, China
Ming-Yan Fang BGI-Shenzhen, Shenzhen , Guangdong Province, China
Jian-Guo Zhang BGI-Shenzhen, Shenzhen , Guangdong Province, China
Zhen-Fang Du Department of Cell Biology and Medical Genetics, Research Center for Molecular Medicine, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou , Zhejiang Province, China
Xian-Ning Zhang Department of Cell Biology and Medical Genetics, Research Center for Molecular Medicine, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou , Zhejiang Province, China
Hits: 2199
Download times: 141
Abstract:
      AIM: To identify the disease-causing gene mutation in a Chinese pedigree with autosomal dominant cone-rod dystrophy (adCORD).

    METHODS: A southern Chinese adCORD pedigree including 9 affected individuals was studied. Whole-exome sequencing (WES), coupling the Agilent whole-exome capture system to the Illumina HiSeq 2000 DNA sequencing platform was used to search the specific gene mutation in 3 affected family members and 1 unaffected member. After a suggested variant was found through the data analysis, the putative mutation was validated by Sanger DNA sequencing of samples from all available family members.

    RESULTS: The results of both WES and Sanger sequencing revealed a novel nonsense mutation c.C766T (p.Q256X) within exon 5 of CRX gene which was pathogenic for adCORD in this family. The mutation could affect photoreceptor-specific gene expression with a dominant-negative effect and resulted in loss of the OTX tail, thus the mutant protein occupies the CRX-binding site in target promoters without establishing an interaction and, consequently, may block transactivation.

    CONCLUSION: All modes of Mendelian inheritance in CORD have been observed, and genetic heterogeneity is a hallmark of CORD. Therefore, conventional genetic diagnosis of CORD would be time-consuming and labor-intensive. Our study indicated the robustness and cost-effectiveness of WES in the genetic diagnosis of CORD.

PMC FullText Html:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4651873/
PDF Fulltext  Download reader  HTML Fulltext   View/Add Comment