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Novel mutations in the folliculin gene associated with spontaneous pneumothorax

¹ Pulmonary Division, ⁴ Institute of Diagnostic Radiology, University Hospital of Zurich, ² Division of Medical Molecular Genetics and Gene Diagnostics, Institute of Medical Genetics, University of Zurich, Zurich, Switzerland, and ³ Institut de la Vision, INSERM U592, Université Pierre et Marie Curie6, Paris, France.

CORRESPONDENCE: E. W. Russi, Pulmonary Division, University Hospital, Raemistrasse 100, CH-8091 Zurich, Switzerland. Fax: 41 442554451. E-mail: erich.russi{at}usz.ch

Keywords: Familial pneumothorax, folliculin gene, mutation, pneumothorax

Received: October 9, 2007
Accepted June 12, 2008

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.