BARDET-BIEDL SYNDROME - A MOLECULAR AND PHENOTYPIC STUDY OF 18 FAMILIES

The autosomal recessive disorder Bardet-Biedl syndrome is characterise d by retinal degeneration, polydactyly, obesity, mental retardation, h ypogenitalism, renal dysplasia, and short stature. It is heterogeneous with at least four gene loci (BBS1-4) having been mapped to date. We have studied 18 multiply affected families noting the presence of both major and minor manifestations. Using a fluorescently based PCR techn ique, we genotyped each family member and assigned linkage to one of t he four loci. Given this degree of heterogeneity we hoped to find phen otypic differences between linkage categories. We found 44% of familie s linked to 11q13 (BBS1) and 17% linked to 16q21 (BBS2). Only one fami ly was linked to 15q22 (BBS4) and none to 3p12. We conclude that BBS1 is the major locus among white Bardet-Biedl patients and that BBS3 is extremely rare. Only subtle phenotypic differences were observed, the most striking of which was a finding of taller affected offspring comp ared with their parents in the BBS1 category. Affected subjects in the BBS2 and 4 groups were significantly shorter than their parents. Twen ty eight percent of pedigrees did not show linkage to any known locus, evidence for at least a fifth gene. We conclude that the different ge nes responsible for Bardet-Biedl syndrome may influence growth charact eristics such as height.