{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T03:55:13Z","timestamp":1771559713308,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2016,8,17]],"date-time":"2016-08-17T00:00:00Z","timestamp":1471392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["(NIAMS) R01AR062651"],"award-info":[{"award-number":["(NIAMS) R01AR062651"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1AR066124"],"award-info":[{"award-number":["RO1AR066124"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000912","name":"March of Dimes Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000912","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:sec><jats:label\/><jats:p>Dominant mutations in <jats:italic>TRPV4<\/jats:italic>, which encodes the Transient Receptor Potential Cation Channel Subfamily V Member 4 calcium channel, result in a series of musculoskeletal disorders that include a set of peripheral neuropathies and a broad phenotypic spectrum of skeletal dysplasias. The skeletal phenotypes range from brachyolmia, in which there is scoliosis with mild short stature, through perinatal lethal metatropic dysplasia. We describe a case with phenotypic findings consistent with metatropic dysplasia, but in whom no <jats:italic>TRPV4<\/jats:italic> mutation was detected by Sanger sequence analysis. Exome sequence analysis identified a known lethal metatropic dysplasia mutation, <jats:italic>TRPV4<\/jats:italic><jats:sup>L618P<\/jats:sup>, which was present at lower frequency than would be expected for a heterozygous change. The affected individual was shown to be a somatic mosaic for the mutation, providing an explanation for the milder than expected phenotype. The data illustrate that high\u2010throughput sequencing of genomic DNA can facilitate detection of mosaicism with higher sensitivity than Sanger sequence analysis and identify a new genetic mechanism for metatropic dysplasia. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37942","type":"journal-article","created":{"date-parts":[[2016,8,17]],"date-time":"2016-08-17T11:02:54Z","timestamp":1471431774000},"page":"3298-3302","source":"Crossref","is-referenced-by-count":11,"title":["Somatic mosaicism for a lethal <i>TRPV4<\/i> mutation results in non\u2010lethal metatropic dysplasia"],"prefix":"10.1002","volume":"170","author":[{"given":"Michael M.","family":"Weinstein","sequence":"first","affiliation":[{"name":"Department of Molecular, Cell, and Developmental Biology University of California Los Angeles Los Angeles"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taekyu","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics University of California Los Angeles Los Angeles"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralph S.","family":"Lachman","sequence":"additional","affiliation":[{"name":"International Skeletal Dysplasia Registry University of California Los Angeles Los Angeles"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Bamshad","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences University of Washington Seattle"},{"name":"University of Washington Center for Mendelian Genomics University of Washington Seattle"},{"name":"Department of Pediatrics University of Washington Seattle"},{"name":"Division of Genetic Medicine Seattle Children's Hospital Seattle"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah A.","family":"Nickerson","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences University of Washington Seattle"},{"name":"University of Washington Center for Mendelian Genomics University of Washington Seattle"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"Krakow","sequence":"additional","affiliation":[{"name":"International Skeletal Dysplasia Registry University of California Los Angeles Los Angeles"},{"name":"Department of Human Genetics David Geffen School of Medicine at UCLA Los Angeles"},{"name":"Department of Orthopaedic Surgery David Geffen School of Medicine at UCLA Los Angeles"},{"name":"Orthopaedic Hospital Research Center David Geffen School of Medicine at UCLA Los Angeles"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel H.","family":"Cohn","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell, and Developmental Biology University of California Los Angeles Los Angeles"},{"name":"International Skeletal Dysplasia Registry University of California Los Angeles Los Angeles"},{"name":"Department of Orthopaedic Surgery David Geffen School of Medicine at UCLA Los Angeles"},{"name":"Orthopaedic Hospital Research Center David Geffen School of Medicine at UCLA Los Angeles"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,8,17]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.508"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33392"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.08.010"},{"key":"e_1_2_5_5_1","first-page":"591","article-title":"Recurrence of lethal osteogenesis imperfecta due to parental mosaicism for a dominant mutation in a human type I collagen gene (COL1A1)","volume":"46","author":"Cohn DH","year":"1990","journal-title":"Am J Hum Genet"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.509"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34223"},{"key":"e_1_2_5_8_1","unstructured":"ExAC. Exome Aggregation Consortium URL:http:\/\/exac.broadinstitute.org Accessed April2016."},{"key":"e_1_2_5_9_1","unstructured":"GATK. Genome Analysis Toolkit URL:http:\/\/www.broadinstitute.org\/gatk Accessed April2016."},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.01.021"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.512"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2016.01.002"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.166"},{"key":"e_1_2_5_14_1","unstructured":"SchindlerA SumnerC Hoover\u2010FongJE.2014. TRPV4\u2010associated disorders. In: GeneReviews at GeneTests Medical Genetics Information Resource (database online). Copyright University of Washington Seattle. 1997\u20132013. Available athttp:\/\/www.genetests.org. 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