Birt-Hogg-Dubé (BHD) syndrome is a rare inherited genodermatosis characterized by
hair follicle hamartomas, kidney tumors, and spontaneous pneumothorax. Recombination
mapping in BHD families delineated the susceptibility locus to 700 kb on chromosome
17p11.2. Protein-truncating mutations were identified in a novel candidate gene in
a panel of BHD families, with a 44% frequency of insertion/deletion mutations within
a hypermutable C(8) tract. Tissue expression of the 3.8 kb transcript was widespread,
including kidney, lung, and skin. The full-length BHD sequence predicted a novel protein,
folliculin, that was highly conserved across species. Discovery of disease-causing
mutations in BHD, a novel kidney cancer gene associated with renal oncocytoma or chromophobe
renal cancer, will contribute to understanding the role of folliculin in pathways
common to skin, lung, and kidney development.