Home > Archive>Volume 8, Issue 6, 2015 >1112-1117. DOI:10.3980/j.issn.2222-3959.2015.06.06
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A novel CRX mutation by whole-exome sequencing in an autosomal dominant cone-rod dystrophy pedigree
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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).

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    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.

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Qin-Kang Lu, Na Zhao, Ya-Su Lv,/et al.A novel CRX mutation by whole-exome sequencing in an autosomal dominant cone-rod dystrophy pedigree. Int J Ophthalmol, 2015,8(6):1112-1117

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Publication History
  • Received:January 27,2015
  • Revised:March 30,2015
  • Online: November 12,2015
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