Genetic analysis of Chinese families reveals a novel truncation allele of the retinitis pigmentosa GTPase regulator gene

• Main Authors: Fang Hu, Xiang-Yun Zeng, Lin-Lin Liu, Yao-Ling Luo, Yi-Ping Jiang, Hui Wang, Jing Xie, Cheng-Quan Hu, Lin Gan, Liang Huang
• Format: Article
• Language: English
• Published: Press of International Journal of Ophthalmology (IJO PRESS) 2014-10-01
• Series: International Journal of Ophthalmology
• Subjects: retinitis pigmentosa GTPase regulator; retinitis pigmentosa; next-generation sequencing; genetic diagnosis
• Online Access: http://www.ijo.cn/en_publish/2014/5/20140502.pdf
• ISSN: 2222-3959; 2227-4898

<b>AIM:</b> To make comprehensive molecular diagnosis for retinitis pigmentosa (RP) patients in a consanguineous Han Chinese family using next generation sequencing based Capture-NGS screen technology. <b>METHODS:</b> A five-generation Han Chinese family diagnosed as non-syndromic X-linked recessive RP (XLRP) was recruited, including four affected males, four obligate female carriers and eleven unaffected family members. Capture-NGS was performed using a custom designed capture panel covers 163 known retinal disease genes including 47 RP genes, followed by the validation of detected mutation using Sanger sequencing in all recruited family members. <b>RESULTS:</b> Capture-NGS in one affected 47-year-old male reveals a novel mutation, c.2417_2418insG:p.E806fs, in exon ORF15 of RP GTPase regulator (RPGR) gene results in a frameshift change that results in a premature stop codon and a truncated protein product. The mutation was further validated in three of four affected males and two of four female carriers but not in the other unaffected family members. <b>CONCLUSION:</b> We have identified a novel mutation, c.2417_2418insG:p.E806fs, in a Han Chinese family with XLRP. Our findings expand the mutation spectrum of RPGR and the phenotypic spectrum of XLRP in Han Chinese families, and confirms Capture-NGS could be an effective and economic approach for the comprehensive molecular diagnosis of RP.