Salivary gland tumors that developed in BHD patients exhibited an upregulated mTOR-S6R pathway as well as increased GPNMB expression, which are characteristics of FLCN-deficient cells.
Birt-Hogg-Dubé (BHD) syndrome is associated with the development of hereditary renal cell carcinoma (RCC) and is caused by a germline mutation in the folliculin gene.
The literature has reported cases diagnosed with familial PSP, who have no manifestations of Birt-Hogg-Dubé (BHD) syndrome but mutations in different exons of the Folliculin (FLCN) gene.
These findings suggest that the decreased FLCN expression itself without producing mutated folliculin proteins can be at risk for developing clinical manifestations of BHDS: fibrofolliculomas, lung cysts, and tumorigenesis in the kidneys.
The diagnosis of BHDS was established by folliculin (FLCN) genetic testing, and the results were compared to the histopathological findings of FFs or trichodiscomas (TDs).
The Birt-Hogg-Dubé (BHD) syndrome related protein FLCN has recently been implicated in the vesicular trafficking processes by interacting with several Rab family GTPases.
Ongoing research efforts are focused on clarifying the primary FLCN-associated pathway(s) that drives the development of fibrofolliculomas, lung cysts and kidney tumors in BHD patients carrying germline FLCN mutations.
Birt-Hogg-Dubé syndrome (BHD, also referred to as Hornstein-Knickenberg syndrome) is an autosomal dominant tumor syndrome caused by mutations in the FLCN gene located on chromosome 17.
Genetic investigations revealed constitutional mutations in FLCN, associated with Birt-Hogg-Dubé syndrome (BHD) and CCM2, associated with familial cerebral cavernous malformation.
Mutations in the FLCN gene are the cause of Birt-Hogg-Dubé syndrome, a rare tumor syndrome which is characterized by the combination of renal cell carcinoma, pneumothorax and skin tumors.
Germline H255Y and K508R missense mutations in the folliculin (FLCN) gene have been identified in patients with bilateral multifocal (BMF) kidney tumours and clinical manifestations of Birt-Hogg-Dubé (BHD) syndrome, or with BMF kidney tumours as the only manifestation; however, their impact on FLCN function remains to be determined.
In this study, we report the identification of 13 variants and three polymorphisms in the FLCN gene in 143 Danish patients or families with suspected BHD syndrome.