title: Genotype and Phenotype Studies in Autosomal Dominant Retinitis Pigmentosa (adRP) of the French Canadian Founder Population.
abstract: OBJECTIVE
  The French Canadian population of Quebec is a unique, well-known founder population with religious, linguistic, and geographic isolation. The genetics of retinitis pigmentosa (RP) in Quebec is not well studied thus far. The purpose of our study was to establish the genetic architecture of autosomal dominant RP (adRP) and to characterize the phenotypes associated with new adRP mutations in Quebec.
  
  
  METHODS
  Sanger sequencing of the commonly mutated currently known adRP genes was performed in a clinically well-characterized cohort of 60 adRP French Canadian families. Phenotypes were analyzed by projected visual acuity (best corrected), Goldmann visual fields, optical coherence tomography (OCT), fundus autofluorescence (FAF), and ERG. The potential effect of the novel mutations was assessed using in silico bioinformatic tools. The pathogenicity of all variants was then confirmed by segregation analysis within the families, when available.
  
  
  RESULTS
  We identified the causal mutation/gene in 24 of our adRP families, as 24 (40%) of 60 patients had adRP mutations in six known adRP genes. Eleven (46%) of these mutations were in RHO, four mutations (17%) were found in SNRNP200, three mutations (12.5%) in PRPH2/RDS, three mutations (12.5%) in TOPORS, two mutations (8%) in PRPF31, and one mutation (4%) in IMPDH1. Four mutations were novel. We identified new mutations in RHO (p.S270I), PRPF31 (p.R288W), IMPDH1 (p.Q318H), and TOPORS (p.H889R); the rest were previously reported. We present the genotype-phenotype characteristics of the four novel missense mutations.
  
  
  CONCLUSIONS
  This is the first large screening of adRP genes in the founder population of Quebec. Our prevalence of known adRP genes is 40% in the French Canadian population, which is lower than in other adRP populations around the world, illustrating the uniqueness of 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 our founder population.
authors.affiliation: The McGill Ocular Genetics Laboratory Paediatric Ophthalmology Division, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Razek Georges
authors.initials: RG
authors.lastname: Coussa
authors.affiliation: UCL-Institute of Ophthalmology, London, United Kingdom.
authors.forename: Christina
authors.initials: C
authors.lastname: Chakarova
authors.affiliation: The McGill Ocular Genetics Laboratory Paediatric Ophthalmology Division, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Radwan
authors.initials: R
authors.lastname: Ajlan
authors.affiliation: The McGill Ocular Genetics Laboratory Paediatric Ophthalmology Division, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Taha
authors.affiliation: The McGill Ocular Genetics Laboratory Paediatric Ophthalmology Division, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Conrad
authors.initials: C
authors.lastname: Kavalec
authors.affiliation: The McGill Ocular Genetics Laboratory Paediatric Ophthalmology Division, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Julius
authors.initials: J
authors.lastname: Gomolin
authors.affiliation: The McGill Ocular Genetics Laboratory Paediatric Ophthalmology Division, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Khan
authors.affiliation: The McGill Ocular Genetics Laboratory Paediatric Ophthalmology Division, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Irma
authors.initials: I
authors.lastname: Lopez
authors.affiliation: The McGill Ocular Genetics Laboratory Paediatric Ophthalmology Division, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Huanan
authors.initials: H
authors.lastname: Ren
authors.affiliation: UCL-Institute of Ophthalmology, London, United Kingdom.
authors.forename: Naushin
authors.initials: N
authors.lastname: Waseem
authors.affiliation: Department of Cellular Therapy and Regenerative Medicine, CSIC-CABIMER, Seville, Spain.
authors.forename: Kunka
authors.initials: K
authors.lastname: Kamenarova
authors.affiliation: UCL-Institute of Ophthalmology, London, United Kingdom.
authors.forename: Shomi S
authors.initials: SS
authors.lastname: Bhattacharya
authors.affiliation: The McGill Ocular Genetics Laboratory Paediatric Ophthalmology Division, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Koenekoop
mesh_terms: D000328:Adult; D000368:Aged; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D015995:Prevalence; D011792:Quebec / Q000453:epidemiology; D012174:Retinitis Pigmentosa / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism
chemical_list: D005136:Eye Proteins; D004247:DNA