Background:Primary spontaneous pneumothorax (PSP) is a common manifestation of Birt-Hogg-Dubé (BHD) syndrome,which is an autosomal dominant disorder caused by mutation of the folliculin (FLCN) gene.This study was established to investigate the mutation of the FLCN gene and the phenotype in a family with PSP.Methods:We investigated the clinical and genetic characteristics of a large Chinese family with recurrent spontaneous pneumothorax.Genetic testing was performed by Sanger sequencing of the coding exons (4-14 exons) of the FLCN gene.Results:Among ten affected members in a multi-generational PSP kindred,with a total of 18 episodes of spontaneous pneumothorax,the median age for the initial onset of pneumothorax was 42.5 years (interquartile range:28.8-57.2 years).Chest computed tomography scan of the proband showed pulmonary cysts and pneumothorax.A novel nonsense mutation (c.1273C＞T) in exon 11 of FLCN gene that leads to a pre-mature stop codon (p.Gln425*) was identified in the family.The genetic analysis confirmed the diagnosis of BHD syndrome in this family in the absence of skin lesions or renal rumors.Conclusions:A novel nonsense mutation of FLCN gene was found in a large family with PSP in China.Our results expand the mutational spectrum of FLCN gene in patients with BHD syndrome.