A novel missense variant c.G644A (p.G215E) of the RPGR gene in a Chinese family causes X-linked retinitis pigmentosa.

Jiewen Fu,Jingliang Cheng,Chunli Wei,Qi Zhou,Hongbin Lv,Hanchun Chen,Junjiang Fu

doi:10.1042/bsr20192235

Abstract

The mutations in patients with X-linked retinitis pigmentosa (xlRP) have not been well described in the Chinese population. In the present study, a five-generation Chinese retinitis pigmentosa (RP) family was recruited; targeted next-generation sequencing (TGS) was used to identify causative genes and Sanger sequencing for co-segregation. RNA-seq data analysis and revere transcriptional-polymerase chain reaction (RT-PCR) were applied to investigate gene expression patterns of RP GTPase regulator (RPGR) in human and Rpgr in mouse. A novel, hemizygous, deleterious and missense variant: c.G644A (p.G215E) in the RPGR gene (NM_000328.2) exon 7 of X-chromosome was identified in the proband, which was co-segregated with the clinical phenotypes in this family. RNA-seq data showed that RPGR is ubiquitously expressed in 27 human tissues with testis in highest, but no eye tissues data. Then the expressions for Rpgr mRNA in mice including eye tissues were conducted and showed that Rpgr transcript is ubiquitously expressed very highly in retina and testis, and highly in other eye tissues including lens, sclera, and cornea; and expressed highly in the six different developmental times of retinal tissue. Ubiquitous expression in different tissues from eye and very high expression in the retina indicated that RPGR plays a vital role in eye functions, particularly in retina. In conclusion, our study is the first to indicate that the novel missense variant c.G644A (p.G215E) in the RPGR gene might be the disease-causing mutation in this xlRP family, expanding mutation spectrum. These findings facilitate better understanding of the molecular pathogenesis of this disease; provide new insights for genetic counseling and healthcare.

Highlights

Retinitis pigmentosa (RP) (OMIM 268000) is a large genetic heterogeneity of inherited ocular diseases that results in a progressive retinal degeneration affecting 1 in 3000–5000 people [1,2,3]
The fundus photographs (FP) and fundus fluorescent photographs (FFP) of the proband in both eyes are shown in the Figure 2
FFP results showed a hyperautofluorescent ring surrounding a central area of hypoautofluorescence and an atrophic macular region (Figure 2,C,D)

Summary

Introduction

Retinitis pigmentosa (RP) (OMIM 268000) is a large genetic heterogeneity of inherited ocular diseases that results in a progressive retinal degeneration affecting 1 in 3000–5000 people [1,2,3]. XlRP is a severe form of inherited retinal degeneration that primarily affects the rod photoreceptors with an early onset of night blindness and progressive reduction in the visual field, often causing patients to become legally blind by the age of 30–40 years [5,6]. RP2 (OMIM 312600) is caused by mutation in the RP2 gene (OMIM 300757). RP23 (OMIM 300424) is caused by mutation in the OFD1 gene (OMIM 300170). The RPGR gene was known as COD1, CORDX1, CRD, orf, PCDX, RP3, RP15, or XLRP3.

Methods

Results

Conclusion