PT  - JOURNAL ARTICLE
AU  - B. A. Fröhlich
AU  - C. Zeitz
AU  - G. Mátyás
AU  - H. Alkadhi
AU  - C. Tuor
AU  - W. Berger
AU  - E. W. Russi
TI  - Novel mutations in the folliculin gene associated with spontaneous pneumothorax
AID  - 10.1183/09031936.00132707
DP  - 2008 Nov 01
TA  - European Respiratory Journal
PG  - 1316--1320
VI  - 32
IP  - 5
4099  - http://erj.ersjournals.com/content/32/5/1316.short
4100  - http://erj.ersjournals.com/content/32/5/1316.full
SO  - Eur Respir J2008 Nov 01; 32
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.