TY  - CHAP
M1  - Book, Section
TI  - The Birt-Hogg-Dubé Syndrome
A1  - Schmidt, Laura S.
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
Y1  - 2019
N1  - 10.1036/ommbid.345
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - The  phenotypic  features  of  the  Birt-Hogg-Dubé  syndrome  (BHD)  (OMIM#135150)  are  benign  tumors  of  the  hair  follicle  (fibrofolliculomas),  spontaneous  pneumothorax,  and  an  increased  risk  for  developing  renal  tumors.  The  BHD  syndrome  is  inherited  in  an  autosomal  dominant  pattern.  Fibrofolliculomas  are  pilar  hamartomas  characterized  by  proliferation  of  both  epithelial  and  fibrous  tissue.BHD  patients  are  predisposed  to  develop  renal  carcinomas.  Renal  tumors  may  be  solitary  or  multiple  and  bilateral.  All  histologic  types  of  renal  carcinoma  occur  in  BHD  patients.  The  most  common  type  found  in  association  with  the  BHD  syndrome  is  a  hybrid  oncocytic  tumor  with  features  of  both  renal  oncocytoma  and  chromophobe  renal  carcinoma.BHD  is  caused  by  germline  mutations  in  the  FLCN  gene,  located  at  chromosome  17p11.2.  FLCN  encodes  a  novel  protein,  folliculin,  that  has  no  characteristic  domains  to  suggest  function  but  is  conserved  across  species.  FLCN  is  widely  expressed  in  multiple  tissues,  and  alternative  transcripts  have  been  reported.The  majority  of  germline  mutations  in  the  FLCN  gene  are  frameshift,  nonsense  or  splice  site  mutations  that  are  predicted  to  truncate  the  protein.  The  most  frequent  mutation  is  a  cytosine  insertion  or  deletion  in  a  hypermutable  C8  tract  within  exon  11  of  the  FLCN  gene.Loss  or  mutational  inactivation  of  the  wild  type  copy  of  FLCN  in  BHD-associated  renal  tumors,  and  loss  of  tumorigenic  properties  of  a  FLCN-null  renal  tumor  cell  line  upon  FLCN  re-expression  support  a  tumor  suppressor  role  for  FLCN.Although  the  mechanism  by  which  FLCN  inactivation  leads  to  BHD  syndrome  remains  unclear,  research  findings  with  FLCN-deficient  in  vitro  and  in  vivo  models  suggest  that  FLCN  may  be  involved  in  modulating  mTOR  signaling  and  potentially  in  other  pathways  as  well.Genetic  testing  for  FLCN  should  include  DNA  sequencing,  and  in  those  patients  for  whom  DNA  sequencing  is  mutation-negative,  the  multiple  ligation-dependent  probe  amplification  assay  (MLPA)  or  real-time  quantitative  PCR  (RQ-PCR)  methods  to  detect  large  intragenic  deletions  or  duplications.  Annual  or  biannual  surveillance  by  abdominal  MRI  or  CT  screening  is  recommended  for  at-risk  BHD  family  members  for  early  detection  and  management  of  kidney  tumors.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
M3  - doi: 10.1036/ommbid.345
Y2  - 2024/04/19
UR  - ommbid.mhmedical.com/content.aspx?aid=1181415594
ER  -