Dominant TRPV4 mutations in nonlethal and lethal metatropic dysplasia.

ABSTRACT: Metatropic dysplasia is a clinical heterogeneous skeletal dysplasia characterized by short extremities, a short trunk with progressive kyphoscoliosis, and craniofacial abnormalities that include a prominent forehead, midface hypoplasia, and a squared-off jaw. Dominant mutations in the gene encoding TRPV4, a calcium permeable ion channel, were identified all 10 of a series of metatropic dysplasia cases, ranging in severity from mild to perinatal lethal. These data demonstrate that the lethal form of the disorder is dominantly inherited and suggest locus homogeneity in the disease. Electrophysiological studies demonstrated that the mutations activate the channel, indicating that the mechanism of disease may result from increased calcium in chondrocytes. Histological studies in two cases of l

SUBMITTER: Camacho N 

PROVIDER: S-EPMC4169191 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature