Thus, while other factors are at play, our results are consistent with the increased TRPV4 basal activity being a critical determinant of the severity of skeletal dysplasia.
Finally, a small number of patients have been identified in whom a TRPV4 mutation results in a phenotype combining skeletal dysplasia with peripheral neuropathy.
Taken together, these data strongly support that up-regulation of FST in chondrocytes by skeletal dysplasia-inducing TRPV4 mutations contributes to disease pathogenesis.
Metatropic dysplasia is a rare osteochondrodysplasia due to mutations in the TRPV4 gene: TRPV4 is a cation channel, non-selectively permeable to calcium, encoded by a gene on chromosome 12q24.11; it is widely expressed and involved in many different physiological processes through responses to several different stimuli (physical, chemical, and hormonal) in ciliated epithelial cells.