Abstract

Spontaneous pneumothorax (SP) is mostly sporadic but may also occur in families with genetic disorders such as Birt-Hogg-Dubé syndrome (BHDS), which is caused by mutations in the folliculin gene FLCN.To investigate the presence and type of mutation in a Swiss pedigree and in a sporadic case.Clinical examination, lung function tests and HRCT. 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.We identified two novel mutations in FLCN. Three investigated family members with a history of at least one SP 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 to 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 the CT showed similar bilateral cysts as observed in the two members of the unrelated Swiss family.Mutations in FLCN are associated with cystic lung lesions in an otherwise morphological normal lung and predispose to SP.