Mutations Causing Retinitis Pigmentosa in Gypsy Families

Abstract

Purpose: : To identify the disease–causing mutations in two large Gypsy pedigrees with a severe X–linked (xlRP) and an autosomal dominant (adRP) form of retinitis pigementosa (RP) with partial penetrance.

Methods: : Three generation RP family of Gypsy origin with an autosomal dominant mode of inheritance with partial penetrance was ascertained. Detailed clinical and pedigree information was obtained and full ophthalmological examination performed on 11 members of the family. A second, six generation family of the same origin, showing X–linked mode of inheritance was identified and 30 members were fully clinically examined. The 14 exons including their exon/intron boundaries of PRPF31 were amplified by polymerase chain reaction (PCR) in each individual from the adRP family. The same was performed in the X–linked family for both genes known to cause X–linked RP – XRP2 and RPGR.

Results: : Analysis of the complete coding sequence of PRPF31 in the adRP family led to the identification of a new heterozygous splice site mutation IVS6+1G>T. The retention of exon 6 in the splicing process would result in a truncated protein of 186 amino acids (G176fsX186). RPGR mutation screening in affected male individuals in the X–linked RP family identified a heterozygous c.ORF15+652_653delAG mutation. Interestingly this mutation was found in a homozygous state in one severely affected female from the family.

Conclusions: : This is the first report of molecular genetic analysis of retinitis pigmentosa in Gypsy families, describing a novel PRPF31 mutation and the first case of a homozygous mutation in the RPGR gene in a female individual.

Keywords: gene screening • photoreceptors • retinal degenerations: hereditary