title: The puzzle of TRPV4 channelopathies.
abstract: Hereditary channelopathies, that is, mutations in channel genes that alter channel function and are causal for the pathogenesis of the disease, have been described for several members of the transient receptor potential channel family. Mutations in the TRPV4 gene, encoding a polymodal Ca(2+) permeable channel, are causative for several human diseases, which affect the skeletal system and the peripheral nervous system, with highly variable phenotypes. In this review, we describe the phenotypes of TRPV4 channelopathies and overlapping symptoms. Putative mechanisms to explain the puzzle, and how mutations in the same region of the channel cause different diseases, are discussed and experimental approaches to tackle this surprising problem are suggested.
authors.affiliation: KU Leuven, Department of Cellular & Molecular Medicine, Laboratory of Ion Channel Research, Campus Gasthuisberg, Leuven, Belgium. bernd.nilius@med.kuleuven.be
authors.forename: Bernd
authors.initials: B
authors.lastname: Nilius
authors.forename: Thomas
authors.initials: T
authors.lastname: Voets
mesh_terms: D000818:Animals; D001848:Bone Diseases, Developmental / Q000235:genetics / Q000378:metabolism; D053447:Channelopathies / Q000235:genetics* / Q000378:metabolism; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009140:Musculoskeletal Diseases / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D010641:Phenotype; D050916:TRPV Cation Channels / Q000235:genetics*
chemical_list: D050916:TRPV Cation Channels; C416986:TRPV4 protein, human