Genetic heterogeneity of Bardet-Biedl syndrome in a distinct Canadian population: Evidence for a fifth locus

Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive disease characte rized by retinal dystrophy, renal structural abnormalities, obesity, dysmor phic extremities, and hypogenitalism in males. BBS is genetically heterogen eous with four known loci: BBS1 (11q), BBS2 (16q), BBS3 (3p), and BBS4 (15q ). The prevalence of BBS in Newfoundland is approximately 10-fold greater t han in Switzerland (1:160,000) and similar to the prevalence among the Bedo uin of Kuwait (1:13,500). A population-based genetic survey was performed o n 17 BBS families from the island portion of the province of Newfoundland, a comparatively isolated region of Canada. The families in the study had a total of 36 well-documented, affected individuals with 12 families having 2 or more affected individuals. Linkage at each of the four known loci was t ested with two-point linkage and haplotype analysis. Three of the 17 kindre ds showed linkage to 11q, 1 to 16q, and 1 to 3p. The latter is the first BB S3 family identified in a population of northern European descent. Six fami lies remain undetermined because of poor pedigree structure or inconclusive haplotype analyses. Six families were excluded from all four known BBS loc i, indicating that there is at least a fifth BBS locus (BBS5). (C) 1999 Aca demic Press.