A novel CRX variant (p.R98X) is identified in a Chinese family of Retinitis pigmentosa with atypical and mild manifestations

• Published in: Genes & genomics 2019, 41(3), , pp.359-366
• Main Authors: Zhu, Yingchuan, Tan, Hao, Zeng, Jiarong, Tao, Dachang, Ma, Yongxin, Liu, Yunqiang
• Format: Article
• Language: English
• Subjects: Adult; Animal Genetics and Genomics; Biomedical and Life Sciences; Blindness; Codon, Nonsense; CRX protein; Genes; Haploinsufficiency; HEK293 Cells; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Human Genetics; Humans; Life Sciences; Male; Microbial Genetics and Genomics; Mutation; Nonsense mutation; Pedigree; Phenotype; Plant Genetics and Genomics; Research Article; Retina; Retinal degeneration; Retinitis; Retinitis pigmentosa; Retinitis Pigmentosa - genetics; Retinitis Pigmentosa - pathology; Trans-Activators - genetics; Trans-Activators - metabolism; 생물학
• ISSN: 1976-9571; 2092-9293
• DOI: 10.1007/s13258-018-0763-4

Background Retinitis pigmentosa (RP) is the most common form of hereditary retinal degeneration that can cause inherited blindness. RP has extreme genetic and clinical heterogeneity, which brings a major obstacle to obtaining an accurate molecular diagnosis. Objective To analyze the genetic defect in a Chinese family of RP with a few atypical manifestations. Methods Whole-exome sequencing (WES) was applied to identify the disease-associated genes. Sanger sequencing was performed to validate the variants of candidate genes in the patient and his parents. In vitro expression analysis was further conducted to examine the potential biological function of the gene variant. Results A heterozygous nonsense variant c.292C > T (p.R98X) of CRX gene was identified to be present in the affected male. The c.292C > T variant of CRX was absent in all of the searched databases, including the 10,000 Chinese exome database. The nonsense variant was supposed to result in a truncated CRX protein with a destroyed homedomain (HD), which is essential for CRX translation. Interestingly, the following assay showed that the potential truncated protein was not detected, indicating that the variant may cause a loss-of-function mutation of CRX gene. Conclusion We identified a novel heterozygous null mutation in the CRX gene which was the first evidence of a nonsense mutation in the HD domain of CRX. Our finding suggested that the haploinsufficiency mutation of CRX gene contributed to the atypical and mild manifestations of the autosomal dominant RP in the Chinese family.