CANADIAN BARDET-BIEDL-SYNDROME FAMILY REDUCES THE CRITICAL REGION OF BBS3 (3P) AND PRESENTS WITH A VARIABLE PHENOTYPE

There are at least five distinct Bardet-Biedl syndrome (BBS) loci, fou r of which have been mapped: 11q (BBS1), 16q (BBS2), 3p (BBS3), and 15 q (BBS4), A comparative study of the three Arab-Bedouin kindreds used to map the BBS2, BBS3, and BBS4 loci suggests that the variability in the number and severity of clinical manifestations, particularly the p attern of polydactyly, reflects chromosome-specific subtypes of BBS [C armi et al,, 1995a; Am J Med Genet 59:199-203], We describe a Newfound land kindred of northern European descent and confirm the initial find ing of a BBS locus on chromosome 3, However, the ''BBS3 phenotype,'' w hich includes polydactyly of all four limbs and a progression to morbi d obesity, was not observed. Rather, four of the five BBS patients in this family had polydactyly restricted to their feet. The obesity in t hese patients was reversible with caloric restriction and/or exercise, Mental retardation has been considered a major symptom of BBS. Howeve r, formal IQ testing shows that these patients are of average intellig ence. Haplotype analysis reduces the BBS3 critical region to a 6-cM in terval between D3S1595-D3S1753. (C) 1998 Wiley-Liss, Inc.