Phenotype of an X-Linked Retinitis Pigmentosa Family With a Novel Mutation in the RPGR Gene

Abstract

Introduction: : Mounir Benzerroug, Olivier Genevois, Jerome Massy, Laurence Favennec, Xavier Zanlonghi, Fabienne Gerson, Alice Goldenberg, Marc Muraine

Purpose: : To assesses the clinical phenotype in a French family with X-linked retinitis pigmentosa (XLRP) resulting from a novel deletion in the retinitis pigmentosa GTPase regulator (RPGR) gene.Background: Mutations in the gene RPGR are estimated to cause up to 20% of all Caucasian retinitis pigmentosa and up to 75% of cases of X-Linked RP (XLRP). Exon open reading frame 15 (ORF15) is a purine-rich mutation hotspot. Mutations in RPGR ORF15 have also been documented to cause X linked cone-rod dystrophy (XLCORD) and atrophic macular degeneration at an unknown frequency.

Methods: : RPGR mutation analysis was performed in a French family with XLRP, and several individuals from the family were examined clinically.

Results: : The causative mutation in this family was demonstrated to be a deletion of fourteen base-pairs in the exon open reading frame 15 (ORF15). This deletion resulted in a frameshift in exon ORF15. The aberrant mRNA is predicted to produce an RGPR protein with eleven amino acids because of appearance of a premature stop-codon. Clinical studies that included ophthalmological examination and full-field electroretinography showed that this frameshift mutation resulted in a comparatively less severe form of RP.

Conclusions: : Correlation of a causative RPGR genotype with clinical findings in hemizygotes and carrier heterozygotes is an important step toward predictive diagnosis and should assist in the development of gene-based therapies in the future.Text: 1563 characters

Keywords: retina • genetics • gene/expression