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
Michael L Nickerson, Michelle B Warren, Jorge R Toro, Vera Matrosova, Gladys Glenn, Maria L Turner, Paul Duray, Maria Merino, Peter Choyke, Christian P Pavlovich, Nirmala Sharma, McClellan Walther, David Munroe, Rob Hill, Eamonn Maher, Cheryl Greenberg, Michael I Lerman, W Marston Linehan, Berton Zbar, Laura S Schmidt, Michael L Nickerson, Michelle B Warren, Jorge R Toro, Vera Matrosova, Gladys Glenn, Maria L Turner, Paul Duray, Maria Merino, Peter Choyke, Christian P Pavlovich, Nirmala Sharma, McClellan Walther, David Munroe, Rob Hill, Eamonn Maher, Cheryl Greenberg, Michael I Lerman, W Marston Linehan, Berton Zbar, Laura S Schmidt
Abstract
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.
Source: PubMed