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

  • Cancer Cell. 2002 Aug;2(2):157-64. doi: 10.1016/s1535-6108(02)00104-6.
Michael L Nickerson  1 ,  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
Affiliations
  • 1. Laboratory of Immunobiology, Center for Cancer Research, SAIC-Frederick, Inc., National Center for Cancer Research, Frederick, MD 21702, USA.
PMID: 12204536 DOI: 10.1016/s1535-6108(02)00104-6
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.