Birt Hogg Dube (BHD) Syndrome
Clinical features of BHD.
BHD is associated with renal cell carcinoma, cystic lung disease, and facial fibrofolliculomas. Individuals with BHD have a 50 fold higher risk of pneumothorax compared to their health counterpart. BHD is caused by germline loss-of-function mutations in the folliculin (FLCN) gene on the short arm of chromosome 17.
Role of the Henske Lab in BHD research.
Our lab generated the first yeast model of BHD and the first heterozygous mouse model of BHD. We currently use folliculin null cells and mouse models to study BHD. Mice with one allele of FLCN do not have airspace enlargement, however, they tend to have worse lung injury upon ventilation at high tidal volumes, leading to the “stretch hypothesis.” This hypothesis proposes that BHD cysts arise due to defects in cell-cell adhesion, leading to stretch-induced stress, particularly in regions of the lung with larger changes in alveolar volume and at weaker “anchor points” to the pleura. This is supported by the finding that FLCN downregulation leads to increased cell-cell interaction. Our lab also identified the interaction between FLCN and plakophilin 4 (PKP4), indicating that FLCN plays a role in cell-cell adhesion.