Novel Mutations In Autosomal Dominant Retinitis Pigmentosa And Their Prevalence In The French - Canadian Population, A Well - Known Founder Population

Abstract

Purpose: : The French - Canadian population of Quebec is a well-known founder population, with the current 6 million people descending from 8500 forefathers from France. The purpose of our study is to establish the prevalence of adRP mutations in a clinically well-characterised cohort of 60 retinitis pigmentosa (RP) patients collected from the French-Canadian population via direct sequencing of some of the known adRP genes.

Methods: : Detailed phenotypic characterization was performed including precise family history, acuities, visual fields, fundus autofluorescence imaging and optical coherence tomography. For the genetic analysis, genomic DNA from 60 probands was isolated by standard methods. All coding exons and flanking intronic areas of the selected adRP genes were PCR amplified, purified and sequenced.

Results: : Here we present the identification of seven novel mutations in RHO (p.S270I and p.Q344P), PRPF31 (c.-349del, p.R288W), IMPDH1 (p.Q318H), SNRNP200 (p.V708I), and TOPORS (p.H889R). Their pathogenicity was confirmed by segregation analysis within the families and we performed a detailed genotype-phenotype correlation of those patients carrying the mutations.

Conclusions: : To our knowledge this study provides for the first time, a detailed screening of some of the well known adRP genes in a good sized cohort of French-Canadian adRP population. We found the mutations in the adRP genes tested with an approximate prevalence of 30%. This is similar to previously published data in other populations.

Keywords: retina • mutations • genetics