{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T08:32:47Z","timestamp":1768293167148,"version":"3.49.0"},"reference-count":19,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,3,14]],"date-time":"2012-03-14T00:00:00Z","timestamp":1331683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Heterozygous missense mutations of transient receptor potential vanilloid 4 channel (<jats:italic>TRPV4<\/jats:italic>) cause a spectrum of skeletal disorders, including brachyolmia, spondylometaphyseal dysplasia Kozlowski type, metatropic dysplasia, parastremmatic dysplasia, and spondyloepimetaphyseal dysplasia Maroteaux type. Similarly, heterozygous missense mutations of <jats:italic>TRPV4<\/jats:italic> cause a spectrum of peripheral neuropathy, including hereditary motor and sensory neuropathy type IIC, congenital spinal muscular atrophy, and scapuloperoneal spinal muscular atrophy. There are no apparent differences in the amino acid positions affected or type of change predicted by the <jats:italic>TRPV4<\/jats:italic> mutations responsible for the two disease spectrums; nevertheless, no fundamental phenotypic overlap has been shown between the two spectrums. Here, we report on three patients who had both skeletal dysplasia and peripheral neuropathy caused by heterozygous <jats:italic>TRPV4<\/jats:italic> missense mutations. The skeletal and neurologic phenotypes of these patients covered the wide spectrum of reported TRPV4\u2010pathies (disease caused by <jats:italic>TRPV4<\/jats:italic> mutations). The molecular data are complementary, proving that \u201cneuropathic\u201d mutations can cause skeletal dysplasia but also the \u201cskeletopathic\u201d mutations can lead to neuropathies. Our findings suggest that pathogenic mechanisms of TRPV4\u2010pathies in skeletal and nervous systems are not always mutually exclusive and provide further evidence that there is no clear genotype\u2013phenotype correlation for either spectrum. Co\u2010occurrence of skeletal dysplasia and degenerative neuropathy should be kept in mind in clinical practice including diagnostic testing, surgical evaluation, and genetic counseling. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.35268","type":"journal-article","created":{"date-parts":[[2012,3,14]],"date-time":"2012-03-14T18:27:02Z","timestamp":1331749622000},"page":"795-802","source":"Crossref","is-referenced-by-count":51,"title":["TRPV4\u2010pathy manifesting both skeletal dysplasia and peripheral neuropathy: A report of three patients"],"prefix":"10.1002","volume":"158A","author":[{"given":"Tae\u2010Joon","family":"Cho","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazu","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginia","family":"Fano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ok\u2010Hwa","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong Hee","family":"Chae","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Won 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