Your Resource for Birt-Hogg-Dubé Syndrome
The DENN protein module contains a longin domain, a DENN domain and a d-DENN domain. Nookala et al. (2012) identified a DENN module in folliculin (FLCN), the Birt-Hogg-Dube tumour suppressor. The DENN module is believed to be a GEF for Rab-GTPases, although FLCN is believed to act as a GAP for RagC (Tsun et al., … Read more
Contractile fiber type and mitochondrial function are two key factors of skeletal muscle function. However, the exact mechanism for coupling the two remains unknown. The genes encoding type I myosins Myh7/Myh7b regulate muscle fiber type switching by encoding their intronic miRNAs, miR-208b and miR-499. In a new study, Liu et al., 2016 use transgenic mice … Read more
Gupta et al. (2016b) recently published a review about Birt-Hogg-Dubé Syndrome (BHD) exploring the key points and research advances in genetics and pathogenesis, clinical manifestations, diagnosis and disease management. The review introduces BHD and its first descriptions in the 1970s (Hornstein et al., 1975; Birt et al., 1977), then discusses its genetics and pathogenesis with … Read more
Von Hippel–Lindau (VHL) disease is caused by a germline mutation in the VHL gene that leads to the development of several tumors including clear cell renal cell carcinoma (ccRCC) (Maher and Kaelin, 1997). ‘Clear cell’ tumors are characterized by large, proliferating epithelial cells with clear cytoplasm, and a reduced number of cilia. VHL inactivation leads to the stabilization of … Read more
Germline mutations of the folliculin gene are normally responsible for Birt–Hogg–Dubé (BHD) syndrome. The 3D structure of the C-terminal domain of folliculin (FLCN), folliculin-CT, has been previously determined (Nookala et al., 2012). FLCN is a tumor suppressor and a guanine nucleotide exchange factor (GEF) for Rab35. GEF activity of FLCN towards its GTPase might be … Read more
Inherited cancer predisposition is rare and characterized by large phenotypic variability. This variability can be explained by factors such as allelic heterogeneity, environmental effects or the presence of mutations on two or more inherited cancer genes in the same individual. Considering that inherited mutations are thought to play a role in about 5-10 % of … Read more
Patients with Birt-Hogg-Dubé (BHD) syndrome usually develop benign hair follicle tumours (BHFTs) which appear as multiple whitish papules developing primarily on the face, neck and torso (Menko et al., 2009). BHFTs such as fibrofolliculomas and trichodiscomas (skin-coloured tumours occurring on the upper body) can be associated with various genetic conditions and their histology is often key to … Read more
Renal cell carcinoma (RCC) is the most common type of kidney cancer and although the majority of cases are sporadic approximately 3% of cases are caused by genetic conditions such as BHD, VHL, HLRCC and TSC (Randall et al., 2014). These inherited forms of RCC have provided great insights into sporadic cancer genetics. BHD patients can develop multiple kidney tumours. In … Read more
Birt-Hogg-Dubé syndrome (BHD) is caused by mutations in the gene encoding folliculin (FLCN). How this leads to the BHD clinical manifestations is not yet clear. Since homozygous mutations of FLCN are lethal in mice, rats and dogs at early embryonic stage (Hasumi et al., 2009), zebrafish is a valuable alternative model to study the developmental … Read more
Heat shock protein-90 (Hsp90) is a molecular chaperone required for folding, stability and activity of many proteins, known as clients, including drivers of tumour initiation, progression and metastasis (Rohl et al. 2013). ATPase binding and hydrolysis is essential for the chaperone function of Hsp90. ATPase function is regulated by other proteins known as co-chaperones. In … Read more