title: A novel CRX mutation by whole-exome sequencing in an autosomal dominant cone-rod dystrophy pedigree.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Ophthalmology Center, Yinzhou People's Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo 315040, Zhejiang Province, China.
authors.forename: Qin-Kang
authors.initials: QK
authors.lastname: Lu
authors.affiliation: Ophthalmology Center, Yinzhou People's Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo 315040, Zhejiang Province, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center for Molecular Medicine, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang Province, China.
authors.forename: Ya-Su
authors.initials: YS
authors.lastname: Lv
authors.affiliation: Ophthalmology Center, Yinzhou People's Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo 315040, Zhejiang Province, China.
authors.forename: Wei-Kun
authors.initials: WK
authors.lastname: Gong
authors.affiliation: Ophthalmology Center, Yinzhou People's Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo 315040, Zhejiang Province, China.
authors.forename: Hui-Yun
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Ophthalmology Center, Yinzhou People's Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo 315040, Zhejiang Province, China.
authors.forename: Qi-Hu
authors.initials: QH
authors.lastname: Tong
authors.affiliation: Ophthalmology Center, Yinzhou People's Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo 315040, Zhejiang Province, China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Lai
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center for Molecular Medicine, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang Province, China.
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Liu
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, Guangdong Province, China.
authors.forename: Ming-Yan
authors.initials: MY
authors.lastname: Fang
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, Guangdong Province, China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center for Molecular Medicine, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang Province, China.
authors.forename: Zhen-Fang
authors.initials: ZF
authors.lastname: Du
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center for Molecular Medicine, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang Province, China.
authors.forename: Xian-Ning
authors.initials: XN
authors.lastname: Zhang
keywords: CRX gene; Sanger sequencing; autosomal dominant cone-rod dystrophy; cone-rod dystrophy; mutation; whole-exome sequencing