Identification of a Novel RPGR Exon ORF15 Mutation in a Family With X-linked Retinitis Pigmentosa

Abstract

To investigate the phenotypic and genotypic characteristics of a novel mutation associated with X-linked retinitis pigmentosa (XLRP). Methods: Six individuals in a family with XLRP were recruited, and clinical examinations were performed. All of the members were genotyped with microsatellite markers at loci that were considered to be associated with XLRP. The retinitis pigmentosa GTPase regulator gene (RPGR) was comprehensively screened using direct polymerase chain reaction sequencing. Results: Genotyping analysis showed that the affected individuals in the family shared a common haplotype with selected markers. The patients demonstrated severe retinal degenerative phenotypes consistent with XLRP. Mu-tational screening of RPGR demonstrated a novel mutation, g.ORF15ϩ1232_1233delGG. Conclusions: We identified a novel mutation in the 3Ј end of a highly repetitive region of exon open reading frame 15 (ORF15) and documented the detailed phenotypes of the patients with XLRP with the mutation. The clinical phenotype was consistent with XLRP, supporting the observation that the mutations in the 3Ј end of the ORF15 coding sequence give rise to XLRP. Clinical Relevance: The mutation in the 3Ј end of the ORF15 coding sequence can lead to a spectrum of phenotypes, and the cone-predominant phenotype-related mutations can be located irregularly in exon ORF15.

Identifying pathogenic genetic background of simplex or multiplex retinitis pigmentosa patients: a large scale mutation screening study

“…All these mutations were not identified in 115 normal controls. The RPGR gene is responsible for X-linked RP or X-linked cone–rod dystrophy 31. The g. ORF15+568_571delAGAG mutation is a frameshift mutation in exon ORF15, a mutation hotspot that harbours 60% of XLRP mutations.…”

Clinical course of cone dystrophy caused by mutations in the RPGR gene

“…A common cause of X-linked retinitis pigmentosa (RP) are mutations in the retinitis pigmentosa GTPase regulator gene ( RPGR; Xp21.1) [3–8] The gene has also been reported in X-linked cone-rod dystrophy (CRD) [9–13] or even in pure CD [3, 14, 15]. Although the clinical course of patients with RPGR mutations and RP has been evaluated [16], how the disease progresses in CD patients is currently unknown.…”

Genotype–Phenotype Analysis of RPGR Variations: Reporting of 62 Chinese Families and a Literature Review

“…The variants and clinical data of patients with RPGR were obtained by searching the literature for the keyword RPGR in three databases: PubMed 11 , Web of Science 12 , and Google Scholar 13 ( Meindl et al, 1996 ; Roepman et al, 1996 ; Andreasson et al, 1997 , 2003 ; Buraczynska et al, 1997 ; Fujita et al, 1997 ; Jacobson et al, 1997 ; Weleber et al, 1997 ; Bauer et al, 1998 ; Fishman et al, 1998a , b ; Miano et al, 1998 , 1999 ; Dry et al, 1999 ; Flaxel et al, 1999 ; Rosenberg et al, 1999 ; Zito et al, 1999 , 2000 , 2003 ; Liu et al, 2000 , 2002 ; Vervoort et al, 2000 ; Guevara-Fujita et al, 2001 ; Yokoyama et al, 2001 ; Zhao et al, 2001 , 2020 ; Aguirre et al, 2002 ; Ayyagari et al, 2002 ; Breuer et al, 2002 ; Demirci et al, 2002 , 2004 , 2005 , 2006 ; Pusch et al, 2002 ; Rozet et al, 2002 ; Yang et al, 2002 , 2014 ; Bader et al, 2003 ; Barnes et al, 2003 ; Iannaccone et al, 2003 , 2008 ; Koenekoop et al, 2003 ; Lorenz et al, 2003 ; Rebello et al, 2003 ; Sharon et al, 2003 ; Wegscheider et al, 2004 ; Adamian et al, 2005 ; Ebenezer et al, 2005 ; Jin et al, 2005 , 2006 , 2007a , b , 2008 ; Wang et al, 2005 ...…”