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.
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.
Laboratory of Immunobiology, Center for Cancer Research, SAIC-Frederick, Inc., National Center for Cancer Research, Frederick, MD 21702, USA.
Michael L
ML
Nickerson
Michelle B
MB
Warren
Jorge R
JR
Toro
Vera
V
Matrosova
Gladys
G
Glenn
Maria L
ML
Turner
Paul
P
Duray
Maria
M
Merino
Peter
P
Choyke
Christian P
CP
Pavlovich
Nirmala
N
Sharma
McClellan
M
Walther
David
D
Munroe
Rob
R
Hill
Eamonn
E
Maher
Cheryl
C
Greenberg
Michael I
MI
Lerman
W Marston
WM
Linehan
Berton
B
Zbar
Laura S
LS
Schmidt
D000595:Amino Acid Sequence; D001483:Base Sequence; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D004970:Estrone / Q000737:chemistry / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D020022:Genetic Predisposition to Disease; D018859:Hair Follicle / Q000473:pathology*; D006222:Hamartoma / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D020161:Physical Chromosome Mapping; D011030:Pneumothorax / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013577:Syndrome
D012333:RNA, Messenger; D004970:Estrone