Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dubé syndrome.
Nickerson ML,
Warren MB,
Toro JR,
Matrosova V,
Glenn G,
Turner ML,
Duray P,
Merino M,
Choyke P,
Pavlovich CP,
Sharma N,
Walther M,
Munroe D,
Hill R,
Maher E,
Greenberg C,
Lerman MI,
Linehan WM,
Zbar B,
Schmidt LS.
Laboratory of Immunobiology, Center for Cancer Research, SAIC-Frederick, Inc., National Center for Cancer Research, Frederick, MD 21702, USA.
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.
PMID: 12204536 [PubMed - indexed for MEDLINE]