RT Journal Article
SR Electronic
T1 Novel mutations in the folliculin gene associated with spontaneous pneumothorax
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1316
OP 1320
DO 10.1183/09031936.00132707
VO 32
IS 5
A1 B. A. Fröhlich
A1 C. Zeitz
A1 G. Mátyás
A1 H. Alkadhi
A1 C. Tuor
A1 W. Berger
A1 E. W. Russi
YR 2008
UL http://erj.ersjournals.com/content/32/5/1316.abstract
AB Spontaneous pneumothorax is mostly sporadic but may also occur in families with genetic disorders, such as Birt–Hogg–Dubé syndrome, which is caused by mutations in the folliculin (FLCN) gene. The aim of the present study was to investigate the presence and type of mutation in a Swiss pedigree and in a sporadic case. Clinical examination, lung function tests and high-resolution computed tomography were performed. All coding exons and flanking intronic regions of FLCN were amplified by PCR and directly sequenced. The amount of FLCN transcripts was determined by quantitative real-time RT-PCR. Two novel mutations in FLCN were identified. Three investigated family members with a history of at least one spontaneous pneumothorax were heterozygous for a single nucleotide substitution (c.779G>A) that leads to a premature stop codon (p.W260X). Quantitative real-time RT-PCR revealed a reduction of FLCN transcripts from the patient compared with an unaffected family member. DNA from the sporadic case carried a heterozygous missense mutation (c.394G>A). Lung function of this patient was normal and computed tomography showed similar bilateral cysts, as observed in the two members of the unrelated Swiss family. Mutations in the folliculin gene are associated with cystic lung lesions in an otherwise morphological normal lung and predispose to spontaneous pneumothorax.