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.
Nickerson
Michael L
ML
Laboratory of Immunobiology, Center for Cancer Research, SAIC-Frederick, Inc., National Center for Cancer Research, Frederick, MD 21702, USA.
Warren
Michelle B
MB
Toro
Jorge R
JR
Matrosova
Vera
V
Glenn
Gladys
G
Turner
Maria L
ML
Duray
Paul
P
Merino
Maria
M
Choyke
Peter
P
Pavlovich
Christian P
CP
Sharma
Nirmala
N
Walther
McClellan
M
Munroe
David
D
Hill
Rob
R
Maher
Eamonn
E
Greenberg
Cheryl
C
Lerman
Michael I
MI
Linehan
W Marston
WM
Zbar
Berton
B
Schmidt
Laura S
LS
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