Nonsense Mutations in Folliculin Presenting as Isolated Familial Spontaneous Pneumothorax in Adults

Abstract

Isolated familial spontaneous pneumothorax can be caused by mutations of the FLCN gene. Because development of a pneumothorax and/or pulmonary blebs may be the earliest or the only clinical manifestation of FLCN mutations, pulmonologists should be alert to the contribution of this gene toward this familial form of emphysema.

Birt-Hogg-Dube Syndrome with Multiple Cysts and Recurrent Pneumothorax: Pathological Findings

“…BHD mRNA is most strongly expressed in the stromal cells (macrophages and fibroblasts) and alveolar macrophages. The hypothesis has been proposed that BHD gene mutation induces dysfunction of macrophages and fibroblasts that induces imbalance among cytokine, chemokine, and protease, which causes inflammation or degeneration of substrates that result in cyst formation (13). The walls of the lung cysts in the present patient were lined with epithelial tissue along with an accumulation of elastic fibers showing elastosis; however, fine granular changes were also present, indicating that some additional mechanism was damaging the elastic fibers.…”

A new locus-specific database (LSDB) for mutations in the folliculin (FLCN) gene

“…The database lists previously published point mutations, deletions, duplications and splice site mutations in the FLCN gene (Bessis et al, 2006;Cho et al, 2008;Frohlich et al, 2008;Gad et al, 2007,Graham et al, 2005Gunji et al, 2007;Imada et al, 2009;Kawasaki et al, 2005;Khoo et al, 2002;Kim et al, 2008;Lamberti et al, 2005;Leter et al, 2008;Murakami et al, 2007;Nickerson et al, 2002;Painter et al, 2005;Palmirotta et al, 2008;Ren et al, 2008;Schmidt et al, 2005;Toro et al, 2008;van Steensel et al, 2007;Woodward et al, 2008). In addition 10 previously unpublished novel mutations/variants are included.…”

“…Germline mutations in the folliculin gene (FLCN) were first identified in BHD patients in 2002 (Nickerson et al, 2002). In addition, FLCN mutations have also been discovered in patients with familial Primary Spontaneous Pneumothorax (PSP; MIM# 173600) and cases presenting with familial clear cell renal carcinoma (FcRCC) in whom other features of BHD have not been noted (Frohlich et al, 2008;Graham et al, 2005;Gunji et al, 2007;Painter et al, 2005;Ren et al, 2008;Woodward et al, 2008) …”

Birt–Hogg–Dubé syndrome: an inherited cause of spontaneous pneumothorax

“…About 11.5% of spontaneous pneumothoraces occur in the context of a positive family history 1 and involve heritable conditions such as α1-antitrypsin deficiency, Marfan syndrome, Ehlers-Danlos syndrome (type IV: vascular type), lymphangioleiomyomatosis (when associated with tuberous sclerosis) and cystic fibrosis. Practice CMAJ • Because a positive family history is found in about 11.5% of patients presenting with a spontaneous pneumothorax, it is important to consider genetically inherited syndromes among the possible causes.…”