Mutation analysis of the FLCN gene in Chinese patients with sporadic and familial isolated primary spontaneous pneumothorax

Abstract

Primary spontaneous pneumothorax (PSP) is a common manifestation of Birt-Hogg-Dubé syndrome caused by folliculin gene (FLCN) mutation, which is also found in isolated familial PSP cases. A complete genetic analysis of FLCN was performed in 102 unrelated Chinese patients with isolated PSP and 21 of their family members. Three novel mutations (c.924_926del, c.1611_1631del and c.1740C>T) and a previously reported mutation (c.1733insC) were identified in five familial and five sporadic PSP patients. Of the 21 family members of patients with PSP including 3 previous considered as sporadic, 4 (19%) had history of at least one episode of PSP and 9 (43%) were FLCN mutant carriers without PSP. Seven of the nine (78%) mutant carriers had pulmonary cysts detected by high-resolution computed tomography (HRCT). Although c.924_926del and c.1611_1631del were found in eight patients from the same geographic district, haplotype analysis demonstrated that they did not share the same affected haplotype, thus excluding common ancestry. This study first demonstrates that FLCN mutation contributes to not only familial but also 'apparently sporadic' patients with isolated PSP. It suggests that mutation analysis and HRCT scan may be recommended for first-degree family members of PSP patients with FLCN mutations, irrespective of their family history status of PSP.

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 In addition 10 previously unpublished novel mutations/variants are included.…”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) …”

Clinical and genetic study of a large Chinese family presented with familial spontaneous pneumothorax

“…Ren et al reported a cohort of patients with spontaneous pneumothorax from China and found that out of 10 unrelated patients with FSP, five patients were confirmed to harbor the FLCN mutation. They also demonstrated that FLCN mutation contributes to not only familial but also apparently sporadic patients with isolated spontaneous pneumothorax (7). Some other single-family reports of FSP from Korea (6), India (16) and the USA (17,18) also found different FLCN gene mutations.…”

Autosomal Recessively Inherited Familial Primary Spontaneous Pneumothorax: A Large Family with Frequent Consanguineous Marriages

“…5,7,8,11 One of the major restrictions of our study is that the molecular genetic analysis of this gene was not performed on our cases with FPSP. Investigating the hereditary mutations in FLCN gene in these cases and their families in prospective studies may contribute to understanding the cause of FPSP that develops within this large family circle that has frequent consanguineous marriages.…”

“…3,4 The genetic and molecular basis of FPSP is still not clearly understood. 5 There is not only genetic but also clinical heterogeneity in FPSP. [6][7][8] The clinical picture of the disease may come to light through the combinations of different organ and system involvements.…”