Renal cancer and malformations in relatives of patients with Bardet-Biedl syndrome

Background. Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder with five loci identified thus far. The spectrum of disease includes divers e malformations of the kidney and lower urinary tract. The incidence of BBS is approximately 1/100 000 with a predicted heterozygote frequency of 1/16 0, and it has been suggested that heterozygotes are at increased risk of ob esity and hypertension. Methods. We describe renal disease in relatives of 109 UK BBS patients. Usi ng PCR with fluorescent microsatellite markers we amplified DNA derived fro m 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 w ith clear cell renal cell carcinoma (CC-RCC). Results. CC-RCC was diagnosed in three of 180 BBS parents and there was los s of heterozygosity at BBS1 (11q13) in the tumour tissue of one of these su bjects. In addition, there was a high incidence of renal agenesis in siblin gs of BBS patients and two BBS families were identified with apparently dom inant inheritance of renal malformations. In one family we were able to dem onstrate that renal malformations segregated with the BBS2 locus (16q21). Conclusions. Since all parents and two-thirds of siblings of BBS patients m ust be heterozygous for BBS mutations, our observations may implicate BBS g enes in the pathogenesis of both renal cancer and malformations, both disor ders of precursor cell growth and differentiation. We suggest these observa tions 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.