BACKGROUND: Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder with five loci identified thus far. The spectrum of disease includes diverse malformations of the kidney and lower urinary tract. The incidence of BBS is approximately 1/100,000 with a predicted heterozygote frequency of 1/160, and it has been suggested that heterozygotes are at increased risk of obesity and hypertension. METHODS: We describe renal disease in relatives of 109 UK BBS patients. Using PCR with fluorescent microsatellite markers we amplified DNA derived from renal tumours of affected parents to determine whether there was loss of heterozygosity at any of four BBS loci and two other gene loci associated with clear cell renal cell carcinoma (CC-RCC). RESULTS: CC-RCC was diagnosed in three of 180 BBS parents and there was loss of heterozygosity at BBS1 (11q13) in the tumour tissue of one of these subjects. In addition, there was a high incidence of renal agenesis in siblings of BBS patients and two BBS families were identified with apparently dominant inheritance of renal malformations. In one family we were able to demonstrate that renal malformations segregated with the BBS2 locus (16q21). CONCLUSIONS: Since all parents and two-thirds of siblings of BBS patients must be heterozygous for BBS mutations, our observations may implicate BBS genes in the pathogenesis of both renal cancer and malformations, both disorders of precursor cell growth and differentiation. We suggest these observations may have important implications for screening potential BBS carriers for kidney disease and may lead to a greater understanding of the aetiology of renal disease in the general population.
BACKGROUND:Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder with five loci identified thus far. The spectrum of disease includes diverse malformations of the kidney and lower urinary tract. The incidence of BBS is approximately 1/100,000 with a predicted heterozygote frequency of 1/160, and it has been suggested that heterozygotes are at increased risk of obesity and hypertension. METHODS: We describe renal disease in relatives of 109 UK BBSpatients. Using PCR with fluorescent microsatellite markers we amplified DNA derived from renal tumours of affected parents to determine whether there was loss of heterozygosity at any of four BBS loci and two other gene loci associated with clear cell renal cell carcinoma (CC-RCC). RESULTS:CC-RCC was diagnosed in three of 180 BBS parents and there was loss of heterozygosity at BBS1 (11q13) in the tumour tissue of one of these subjects. In addition, there was a high incidence of renal agenesis in siblings of BBSpatients and two BBS families were identified with apparently dominant inheritance of renal malformations. In one family we were able to demonstrate that renal malformations segregated with the BBS2 locus (16q21). CONCLUSIONS: Since all parents and two-thirds of siblings of BBSpatients must be heterozygous for BBS mutations, our observations may implicate BBS genes in the pathogenesis of both renal cancer and malformations, both disorders of precursor cell growth and differentiation. We suggest these observations may have important implications for screening potential BBS carriers for kidney disease and may lead to a greater understanding of the aetiology of renal disease in the general population.