Association between Birt Hogg Dube syndrome and cancer predisposition.
The Birt Hogg Dubé syndrome (BHD) is a rare autosomal dominant genodermatosis predisposing patients to developing fibrofolliculoma, trichodiscoma and acrochordon. The syndrome is caused by germline mutations in the folliculin (FLCN) gene, encoding the folliculin tumor-suppressor protein. Numerous mutations have been described in the FLCN gene, the most frequent occurring within a C8 tract of exon 11. This hypermutability is probably due to a slippage in DNA polymerase during replication, resulting in gains/losses of repeat units, causing cancer predisposition. The main phenotypic manifestations related to this disease are lung cysts, leading to pneumothorax, and a 7-fold increased risk for renal neoplasia, although other neoplastic manifestations have been described in BHD-affected individuals. Of particular interest is the often reported genotype/phenotype correlation between FLCN mutations and risk of colon or breast cancer. This paper describes our current knowledge on the association between BHD and cancer predisposition and briefly summarizes our experience in this field.
Palmirotta
Raffaele
R
Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele, Via della Pisana 235, 00163, Rome, Italy. raffaele.palmirotta@sanraffaele.it
Savonarola
Annalisa
A
Ludovici
Giorgia
G
Donati
Pietro
P
Cavaliere
Francesco
F
DE Marchis
Maria Laura
ML
Ferroni
Patrizia
P
Guadagni
Fiorella
F
D003560:Cysts / Q000235:genetics / Q000473:pathology; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012871:Skin Diseases / Q000235:genetics* / Q000473:pathology*; D013577:Syndrome; D025521:Tumor Suppressor Proteins / Q000235:genetics
C476078:FLCN protein, human; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins