A novel pathogenic variant in folliculin identified in a Chinese family with BHD syndrome

This study aimed to investigate FLCN gene variants in Chinese patients presenting with familial spontaneous pneumothorax associated with Birt-Hogg-Dubé syndrome (BHDS). A Chinese family with a history of familial spontaneous pneumothorax linked to BHD was analyzed. Genetic screening of the folliculin (FLCN) gene was conducted using next-generation sequencing (NGS) technology. A nonsense variant (c.439 C > T) in the FLCN gene was identified in six individuals within the family. This variant, previously unreported in the Chinese population, results in the substitution of glutamine at the 147th amino acid position in exon 6 with a premature stop codon. The variant is hypothesized to induce nonsense-mediated mRNA decay, potentially leading to the absence of functional protein expression, which may underlie the pathogenesis of pneumothorax in this family. The findings elucidate the FLCN variant associated with familial spontaneous pneumothorax in BHD, thereby expanding the variantion spectrum of the FLCN gene and providing insights into the molecular mechanisms of this condition.