Fig. 3

Pedigree of this family and the chromatograms of each member (A). Crystal structure model of Human TRPV4. One subunit was shown in green and the rest in grey. Mutation sites related to CMT2C and SPSMA were marked. Only the V620 was located in the transmembrane region. The other sites were located in the ARD region (B). The mutation sites in the ribbon diagram of the ARD region (residues 148–392) were labeled. All of these sites were in the connecting finger loop between the ankyrin repeats (C). Schematic illustration of the TRPV4 protein domains is accompanied with the location of specific phenotype of neuropathy and skeletal dysplasia respectively (D). Skeletal dysplasia was located in the helices, the convex face of TRPV4 ARD, where neuropathy-related mutations have not been described. The phenotypes of TRPV4-related neuropathies were a spectrum from the ventral horn cell to the distal peripheral nerve (E). Black filled symbol = affected; empty symbol = unaffected; empty symbol with black dot = mildly affected mutation carrier in clinical