{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:46:21Z","timestamp":1784180781501,"version":"3.55.0"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,1,28]],"date-time":"2019-01-28T00:00:00Z","timestamp":1548633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014535","name":"Center for Individualized Medicine, Mayo Clinic","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100014535","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Transient receptor potential cation channel subfamily V member 4 (<jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>4) is an ion channel permeable to Ca<jats:sup>2+<\/jats:sup> that is sensitive to physical, hormonal, and chemical stimuli. This protein is expressed in many cell types, including osteoclasts, chondrocytes, and sensory neurons. As such, pathogenic variants of this gene are associated with skeletal dysplasias and neuromuscular disorders. Pathogenesis of these phenotypes is not yet completely understood, but it is known that genotype\u2013phenotype correlations for <jats:italic><jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>4<\/jats:italic> pathogenic variants often are not present.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Newly characterized, suspected pathogenic variant in <jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>4 was analyzed using protein informatics and personalized protein\u2010level molecular studies, genomic exome analysis, and clinical study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This statement is demonstrated in the family of our proband, a 47\u2010year\u2010old female having the novel c.2401A&gt;G (p.K801E) variant of <jats:italic><jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>4<\/jats:italic>. We discuss the common symptoms between the proband, her father, and her daughter, and compare her phenotype to known <jats:italic><jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>4<\/jats:italic>\u2010associated skeletal dysplasias.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Protein informatics and molecular modeling are used to confirm the pathogenicity of the unique <jats:italic><jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>4<\/jats:italic> variant found in this family. Multiple data were combined in a comprehensive manner to give complete overall perspective on the patient disease and prognosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.566","type":"journal-article","created":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T06:10:56Z","timestamp":1548742256000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Protein informatics combined with multiple data sources enriches the clinical characterization of novel <i><scp>TRPV<\/scp>4<\/i> variant causing an intermediate skeletal dysplasia"],"prefix":"10.1002","volume":"7","author":[{"given":"Stephanie L.","family":"Hines","sequence":"first","affiliation":[{"name":"Department of Clinical Genomics Mayo Clinic Jacksonville Florida"},{"name":"Department of General Internal Medicine Mayo Clinic Jacksonville Florida"},{"name":"Center for Individualized Medicine Mayo Clinic Jacksonville Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"John E.","family":"Richter","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics Mayo Clinic Jacksonville Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed N.","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics Mayo Clinic Jacksonville Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jain","family":"Mahim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Johns Hopkins School of Medicine Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paldeep S.","family":"Atwal","sequence":"additional","affiliation":[{"name":"Atwal Clinic Jacksonville Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1055-3069","authenticated-orcid":false,"given":"Thomas R.","family":"Caulfield","sequence":"additional","affiliation":[{"name":"Center for Individualized Medicine Mayo Clinic Jacksonville Florida"},{"name":"Department of Neuroscience Mayo Clinic Jacksonville Florida"},{"name":"Mayo Graduate School, Neurobiology of Disease Mayo Clinic Jacksonville Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,28]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm301280p"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.17.3389"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-017-0174-z"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmgm.2011.04.005"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.24131"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/219515"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003935"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20140321"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2011.07.015"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.401"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27624"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201540514"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22808"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C800184200"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/6968395"},{"issue":"6","key":"e_1_2_13_17_1","first-page":"525","article-title":"The PDBFINDER database: A summary of PDB, DSSP and HSSP information with added value","volume":"12","author":"Hooft R. 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