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I. Ebermann, I. Lopez, M. Bitner-Glindzicz, C. Brown, R. K. Koenekoop, H. J. Bolz; Usher Syndrome in French Canadians From Quebec: A Predominant Founder Mutation in the USH1C Gene Provides the First Genetic Link With the Acadian Population. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1659.
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© ARVO (1962-2015); The Authors (2016-present)
To genetically characterize 15 French Canadian patients from different regions of the province of Quebec who were clinically diagnosed as Usher syndrome type 1.
The French-Canadian population of Quebec of ca. 6 million people descends from ca. 8,500 French settlers who colonized the St. Lawrence River valley between 1608 and 1759. The 2,600 settlers who arrived before 1680 contributed about two thirds of the current gene pool. We hypothesized that one or more founder mutations in USH1 genes may exist in this population. We performed genotyping of polymorphic microsatellite markers closely flanking the seven USH1 loci in parallel with a mutation screening strategy. In case of homozygosity for marker alleles of a specific USH1 locus, the coding region of the corresponding gene was sequenced. Where this approach did not lead to the identification of the genetic subtype, we sequenced the entire coding regions of all USH1 genes. Once a mutation was identified, all other patients were screened for this change.
We found that 60% of cases were due to founder mutations of the USH1C gene, a subtype that is rare outside the Acadian population, and that mutations in other genes (MYO7A/USH1B and USH3A/USH3A), except CDH23, are very rare. The USH1C mutation c.216G>A, previously designated the "Acadian allele" because it accounts for virtually all Acadian cases, represents 40% of disease alleles in Quebec and has a carrier frequency in the general population of 1%. Surprisingly, four additional USH1C mutations were found, including three novel.
Based on our findings, approximately 2.5% of the congenitally deaf children in Quebec are at risk of developing additional retinal degeneration due to homozygosity for the c.216G>A mutation, which has implications for diagnostic and therapeutic management of these children. Although the Acadians and French Canadians from Quebec are descended from French ancestors, Acadians and Quebecois have always been considered genetically distinct. The genetic conditions common in Quebec are generally not found in Acadians, or they are due to different mutations. Our results, however, show that carriers of the c.216G>A-allele haplotype belong to the early founders of both, the Acadian and the Quebec population.
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