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Lu QK, Zhao N, Lv YS, et al. A novel CRX mutation by whole-exome sequencing in an autosomal dominant cone-rod dystrophy pedigree. Int J Ophthalmol. 2015;8(6):1112-7doi: 10.3980/j.issn.2222-3959.2015.06.06.
Lu, Q. K., Zhao, N., Lv, Y. S., Gong, W. K., Wang, H. Y., Tong, Q. H., Lai, X. M., Liu, R. R., Fang, M. Y., Zhang, J. G., Du, Z. F., & Zhang, X. N. (2015). A novel CRX mutation by whole-exome sequencing in an autosomal dominant cone-rod dystrophy pedigree. International journal of ophthalmology, 8(6), 1112-7. https://doi.org/10.3980/j.issn.2222-3959.2015.06.06
Lu, Qin-Kang, et al. "A novel CRX mutation by whole-exome sequencing in an autosomal dominant cone-rod dystrophy pedigree." International journal of ophthalmology vol. 8,6 (2015): 1112-7. doi: https://doi.org/10.3980/j.issn.2222-3959.2015.06.06
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 Dec 18;8(6):1112-7. doi: 10.3980/j.issn.2222-3959.2015.06.06. eCollection 2015. PMID: 26682157; PMCID: PMC4651873.
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Int J Ophthalmol. 2015 Dec 18;8(6):1112-7. doi: 10.3980/j.issn.2222-3959.2015.06.06. eCollection 2015.

A novel CRX mutation by whole-exome sequencing in an autosomal dominant cone-rod dystrophy pedigree.

International journal of ophthalmology

Qin-Kang Lu, Na Zhao, Ya-Su Lv, Wei-Kun Gong, Hui-Yun Wang, Qi-Hu Tong, Xiao-Ming Lai, Rong-Rong Liu, Ming-Yan Fang, Jian-Guo Zhang, Zhen-Fang Du, Xian-Ning Zhang

Affiliations

  1. Ophthalmology Center, Yinzhou People's Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo 315040, Zhejiang Province, China.
  2. 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.
  3. BGI-Shenzhen, Shenzhen 518083, Guangdong Province, China.

PMID: 26682157 PMCID: PMC4651873 DOI: 10.3980/j.issn.2222-3959.2015.06.06

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.

Keywords: CRX gene; Sanger sequencing; autosomal dominant cone-rod dystrophy; cone-rod dystrophy; mutation; whole-exome sequencing

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