Background: Usher syndrome type 1 (USH1) is the leading cause of deafblindness. In most populations, many private mutations are distributed across the five known USH1 genes. We investigated patients from the French Canadian population of Quebec (approximately 6 million people) that descends from about 8,500 French settlers who colonized the St Lawrence River valley between 1608 and 1759. We hypothesized that founder mutations in USH1 genes exist in this population.
Results: We have genetically characterized 15 patients from different regions of Quebec who were clinically diagnosed as USH1. Of these cases, 60% carried mutations of the USH1C gene, a genetic subtype that is rare outside the Acadian population. We have discovered a founder effect of the c.216G>A mutation, which has previously been designated the 'Acadian allele' because it accounts for virtually all Acadian USH1 cases. It represents 40% of disease alleles in Quebec, and a carrier of c.216G>A was identified in the general population. Mutations in other genes, except CDH23, are very rare.
Conclusion: Based on our findings, approximately 0.5% of congenitally deaf children in Quebec are at risk of developing retinal degeneration due to homozygosity for c.216G>A. Although the Acadians and French Canadians from Quebec are descended from French ancestors, they 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 belonged to the early founders of both the Acadian and the Quebec population.