1. Identification of novel X-linked gain-of-function RPGR-ORF15 mutation in Italian family with retinitis pigmentosa and pathologic myopia
- Author
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Vanessa Barbaro, Katia De Nadai, Marzio Chizzolini, Stefano Toppo, Francesco Parmeggiani, Enzo Di Iorio, Enrico Lavezzo, Cristina Parolin, and Giorgio Palù
- Subjects
0301 basic medicine ,Proband ,Male ,DNA Mutational Analysis ,gain-of-function mutation ,Loss of heterozygosity ,Exon ,0302 clinical medicine ,Genes, X-Linked ,Myopia ,Child ,Frameshift Mutation ,Sanger sequencing ,Genetics ,Multidisciplinary ,Retinitis pigmentosa GTPase regulator ,Exons ,Middle Aged ,Penetrance ,Pedigree ,Italy ,symbols ,Female ,X-linked retinitis pigmentosa, pathologic myopia, RPGR gene, exon ORF15, gain-of-function mutation ,RPGR gene ,Retinitis Pigmentosa ,Adult ,Heterozygote ,Genotype ,Biology ,White People ,Article ,Frameshift mutation ,NO ,03 medical and health sciences ,symbols.namesake ,Open Reading Frames ,exon ORF15 ,Retinitis pigmentosa ,medicine ,Humans ,Eye Proteins ,Genetic Association Studies ,Hemizygote ,pathologic myopia ,medicine.disease ,X-linked retinitis pigmentosa ,eye diseases ,Protein Structure, Tertiary ,030104 developmental biology ,030221 ophthalmology & optometry - Abstract
The aim of this study was to describe a new pathogenic variant in the mutational hot spot exon ORF15 of retinitis pigmentosa GTPase regulator (RPGR) gene within an Italian family with X-linked retinitis pigmentosa (RP), detailing its distinctive genotype-phenotype correlation with pathologic myopia (PM). All members of this RP-PM family underwent a complete ophthalmic examination. The entire open reading frames of RPGR and retinitis pigmentosa 2 genes were analyzed by Sanger sequencing. A novel frame-shift mutation in exon ORF15 of RPGR gene (c.2091_2092insA; p.A697fs) was identified as hemizygous variant in the male proband with RP, and as heterozygous variant in the females of this pedigree who invariably exhibited symmetrical PM in both eyes. The c.2091_2092insA mutation coherently co-segregated with the observed phenotypes. These findings expand the spectrum of X-linked RP variants. Interestingly, focusing on Caucasian ethnicity, just three RPGR mutations are hitherto reported in RP-PM families: one of these is located in exon ORF15, but none appears to be characterized by a high penetrance of PM trait as observed in the present, relatively small, pedigree. The geno-phenotypic attributes of this heterozygosity suggest that gain-of-function mechanism could give rise to PM via a degenerative cell-cell remodeling of the retinal structures.
- Published
- 2016