De novo <i>TRPV4</i> Leu619Pro variant causes a new channelopathy characterised by giant cell lesions of the jaws and skull, skeletal abnormalities and polyneuropathy

Abstract

Our findings define a novel polysystemic syndrome due to germline <i>TRPV4</i> p.Leu619Pro and further extend the spectrum of <i>TRPV4</i> channelopathies. They further highlight the convergence of <i>TRPV4</i> mutations on different organ systems leading to complex phenotypes which are further mitigated by possible post-zygotic mosaicism. Treatment of this disorder is challenging, and surgical intervention of the GCLJ worsens the lesions, suggesting the future use of MEK inhibitors and TRPV4 antagonists as therapeutic modalities for unmet clinical needs.