Identification of a novel RPGR mutation associated with X-linked cone-rod dystrophy in a Chinese family

Yafang Wang,Shu Liu,Fenghua Wang,Yuanqi Zhai,Xiaodong Sun,Yang Liu,Wenqiu Wang,Xiaoling Wan

doi:10.1186/s12886-021-02166-0

Abstract

BackgroundCone-rod dystrophy (CORD) is a group of inherited retinal dystrophies, characterized by decreased visual acuity, color vision defects, photophobia, and decreased sensitivity in the central visual field. Our study has identified a novel pathogenic variant associated with X-linked cone-rod dystrophy (XLCORD) in a Chinese family.MethodsAll six family members, including the proband, affected siblings, cousins and female carriers, have underwent thorough ophthalmic examinations. The whole exome sequencing was performed for the proband, followed by Sanger sequencing for spilt-sample validation. A mammalian expression vector (AAV-MCS) with mutated retinitis pigmentosa GTPase regulator (RPGR) sequence was expressed in HEK293 T cells. The mutated protein was verified by Western blotting and immunohistochemistry.ResultsA novel mutation in the RPGR gene (c.2383G > T, p.E795X) is identified to be responsible for CORD pathogenesis.ConclusionsOur findings have expanded the spectrum of CORD-associated mutations in RPGR gene and serve as a basis for genetic diagnosis for X-linked CORD.

Highlights

Cone-rod dystrophy (CORD) is a group of inherited retinal dystrophies, characterized by decreased visual acuity, color vision defects, photophobia, and decreased sensitivity in the central visual field
We reported a Chinese family with four male CORD patients carrying a novel nonsense mutation in the exon ORF15 (c.2383G > T, p.E795X) of retinitis pigmentosa GTPase regulator (RPGR) gene, which broaden the spectrum of RPGR mutations associated with X-linked CORD
The family members were examined by best-corrected visual acuity (BCVA), non-contact tonometer, widefield color fundus imaging, widefield fundus autofluorescence (FAF) and optical coherence tomography (OCT) scans

Summary

Introduction

Cone-rod dystrophy (CORD) is a group of inherited retinal dystrophies, characterized by decreased visual acuity, color vision defects, photophobia, and decreased sensitivity in the central visual field. Inherited retinal dystrophies (IRDs) are a highly heterogeneous group of disorders characterized by progressive dysfunction of photoreceptors and retinal pigment epithelium (RPE) cells. The RPGR gene is a major cause of X-linked CORD cases [4]. Multiple isoforms of RPGR have been detected in the retina with RPGR1–19, which spans 19 exons and encodes an 815-aa. Wang et al BMC Ophthalmology (2021) 21:401 polypeptide, and RPGRORF15, which spans 15 exons plus a part of intron 15 and encodes a 1152-aa polypeptide [5,6,7] as the two major isoforms. Due to the presence of highly repetitive purine-rich sequences, the exon ORF15 (exon ORF15 + part of intron 15) of RPGR is prone to mutagenesis accounting for most XLCORD cases

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