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

摘要

AIM: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.METHODS: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.RESULTS:Capture-NGS in one affected 47-year-old male reveals a novel mutation, c.2417₂418insG:p.E806 fs,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.CONCLUSION:We have identified a novel mutation,c.2417₂418insG:p.E806 fs, 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 aneffective and economic approach for the comprehensive molecular diagnosis of RP.