title: Mutations of the Birt Hogg Dube gene in patients with multiple lung cysts and recurrent pneumothorax.
abstract: BACKGROUND
  Birt-Hogg-Dubé (BHD) syndrome, a rare inherited autosomal genodermatosis first recognised in 1977, is characterised by fibrofolliculomas of the skin, an increased risk of renal tumours and multiple lung cysts with spontaneous pneumothorax. The BHD gene, a tumour suppressor gene located at chromosome 17p11.2, has recently been shown to be defective. Recent genetic studies revealed that clinical pictures of the disease may be variable and may not always present the full expression of the phenotypes.
  
  
  OBJECTIVE
  We hypothesised that mutations of the BHD gene are responsible for patients who have multiple lung cysts of which the underlying causes have not yet been elucidated.
  
  
  METHODS
  We studied eight patients with lung cysts, without skin and renal disease; seven of these patients have a history of spontaneous pneumothorax and five have a family history of pneumothorax. The BHD gene was examined using PCR, denaturing high-performance liquid chromatography and direct sequencing.
  
  
  RESULTS
  We found that five of the eight patients had a BHD germline mutation. All mutations were unique and four of them were novel, including three different deletions or insertions detected in exons 6, 12 and 13, respectively and one splice acceptor site mutation in intron 5 resulting in an in-frame deletion of exon 6.
  
  
  CONCLUSIONS
  We found that germline mutations of the BHD gene are involved in some patients with multiple lung cysts and pneumothorax. Pulmonologists should be aware that BHD syndrome can occur as an isolated phenotype with pulmonary involvement.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Gunji
authors.forename: Taeko
authors.initials: T
authors.lastname: Akiyoshi
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Sato
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kurihara
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tominaga
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Seyama
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003560:Cysts / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D018740:Genetic Heterogeneity; D018095:Germ-Line Mutation; D006801:Humans; D007438:Introns / Q000235:genetics; D007680:Kidney Neoplasms / Q000235:genetics; D008171:Lung Diseases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional / Q000235:genetics; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics; D009928:Organ Specificity; D010375:Pedigree; D010641:Phenotype; D011030:Pneumothorax / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics; D012008:Recurrence; D017384:Sequence Deletion / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics*
chemical_list: C476078:FLCN protein, human; D011506:Proteins; D011518:Proto-Oncogene Proteins; D022821:RNA Splice Sites; D025521:Tumor Suppressor Proteins