So the last several posts, I have been comparing tuberous sclerosis, VHL disease and HLRCC to BHD syndrome, in an effort to compare the similarities hoping this would shed light on BHD. Out of them all, BHD is possibly the less well characterised, both the disease and the genetics. This is probably because since the phenotypic spectrum of the disease is so varied, there is no ‘typical BHD patient’ and an under-diagnosed, rare disease is a lot harder to pin down.

However, from my comparisons (which is of course,  purely academic) it would appear that these four genetic conditions, which all predispose to kidney cancer and incidence of cutaneous lesions on the face/neck region, are intrinsically tied in with the mTOR signalling pathway and HIF signalling. Both of which are huge areas of study.

Encouragingly, whilst compiling an original schematic of folliculin from current and previous publications (link here) we similarly showed that folliculin, the protein affected in BHD syndrome, is implied to act upstream, on or downstream of mTOR, which includes HIF2alpha. Of course, there’s only so much you can do by proxy, but now that we have a firm grounding in the cell signalling pathways folliculin is thought to participate in. So I think it would be a good idea to review the literature regarding functional characterisation of folliculin itself.