The literature data base has been updated with two papers:
Mota-Burgos et al. describe the case of a 54 year-old male who presented in clinic with a stage IIIB melanoma. It was noted that the patient had multiple white facial papules, which were confirmed to be fibrofolliculomas by histopathology. Subsequent genetic testing revealed that the patient harboured a missense FLCN mutation (c.553T>C, p.S185P) thus confirming a diagnosis of BHD. Computerised tomography and abdominal ultrasound ruled out the presence of pulmonary cysts and renal neoplasms, but colonoscopy showed the presence of several colorectal adenomatous polyps. The patient’s daughter had inherited the FLCN mutation and also had facial papules. The authors state that the link between BHD and colorectal polyps or melanoma is unclear, as these tumours are common in the general population. Nevertheless, given that melanomas can be caused by dysregulated mTOR signalling, which has also been observed in BHD-associated cysts and tumours, the authors recommend periodic exhaustive skin examination and excisional biopsy of any suspicious pigmented lesions found in BHD patients.
Lu et al. screened for synthetic lethal targets in FLCN-null cells using an siRNA library targeting phosphatase genes. They found that knock down of the serine phosphatase Slingshot2 (SSH2) induced Caspase 3 and Caspase 7 activity, leading to decreased cell viability specifically in FLCN-null UOK-257 and FTC133 cells, but not in their FLCN-positive isogenic counterparts. RNAi knock down of the related genes SSH1 and SSH3 singly did not cause synthetic lethality, but knock down of these genes in combination with SSH2 potentiated the synthetic lethal phenotype. The SSH proteins are known to work antagonistically with the LIM-kinases to regulate cofilin phosphorylation and interestingly, cofilin phosphorylation was found to be dysregulated in FLCN-null cells compared to FLCN-positive isogeneic cells. Cofilin is a proapoptotic gene and may, the authors suggest, be responsible for the synthetic lethality observed in these experiments. Given these results, the authors also suggest that molecules targeting SSH2 may prove an effective therapy for BHD-associated renal cell carcinomas.
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2 thoughts on “BHD Literature Database Updated”
I think I may bhd( face had multiple white bumps,cyst kidney,polyps colon removed,nodules thyroid, old granulomatous disease lung).
I live in Savannah Georgia.
Where can I go to get tested for bhd?
Someone may have a better answer, but I think the answer has two parts. 1) Your current MD should refer you to someone who has experience in diagnosing and monitoring BHD (sorry, I don’t know who that might include in your area). 2) Your current MD or the specialist would order a genetic test for you from one of the providers listed here