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Razek Georges Coussa, Christina Chakarova, Radwan Ajlan, Conrad Kavalec, Aysha Khan, Irma Lopez, Huanan Ren, Naushin Waseem, Shomi S Bhattacharya, Robert K Koenekoop; Genotype and phenotype studies in autosomal dominant retinitis pigmentosa (adRP) of the French Canadian founder population.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3265.
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© ARVO (1962-2015); The Authors (2016-present)
The French Canadian population of Quebec is a well-known founder population. The genetics of retinitis pigmentosa (RP) in Quebec are still incomplete despite intense studies. The purpose of our study is to establish the genetic architecture of autosomal dominant RP (adRP) and to characterize the phenotypes associated with adRP mutations in Quebec.
Sanger sequencing of known adRP genes to a clinically well-characterised cohort of 60 adRP French Canadian families. Phenotypes were analysed by visual acuity, Goldmann visual fields, OCT, fundus autofluorescence and ERG. The potential effect of the novel mutations was assessed using bioinformatic tools. The pathogenicity of all variants was confirmed by segregation analysis within the families.
We identified the causal mutation/gene in 23 adRP families, as 23/60 patients (38%) had adRP mutations in six known adRP genes. Eleven (48%) of these mutations were in RHO, 4 (18%) in SNRNP200, 3 (13%) in PRPH2/RDS, 3 (13%) in TOPORS, 1 (4%) in PRPF31 and 1 (4%) in IMPDH1. We present the genotype-phenotype characteristics of five novel missense mutations identified in RHO (p.Q344P), PRPF31 (p.R288W), IMPDH1 (p.Q318H), SNRNP200 (p.V708I) and TOPORS (p.H889R). While most patients’ phenotypes exhibited classic RP findings, those with novel mutations were additionally characterised by atypical bull’s eye maculopathies, patchy perimacular lacunar hyperpigmentations and macular holes.
This is the first large screening of adRP genes in the founder population of Quebec. As previously reported in other populations, the prevalence of known adRP genes is about 38% in the French Canadian population. Our findings are crucial in expanding the current understanding of the genotypic-phenotypic spectrum of RP and documenting the genetic architecture of a founder population.
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