{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T19:16:22Z","timestamp":1780773382765,"version":"3.54.1"},"reference-count":14,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,3,27]],"date-time":"2019-03-27T00:00:00Z","timestamp":1553644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>A family with skeletal and craniofacial anomalies is presented. Whole\u2010exome sequencing (WES) analysis indicated a diagnosis of Larsen syndrome, although their clinical presentation does not include the hallmark joint dislocations typically observed in Larsen syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patient consent for the sharing of de\u2010identified clinical and genetic information, along with use of photographs for publication, was obtained.<\/jats:p><jats:p>WES and variant segregation analysis by WES were performed by commercial laboratory, GeneDx (Gaithersburg, MD), on peripheral blood samples from the proband, her brother, and her parents using methods detailed on their website for test<jats:italic>XomeDx Whole Exome Sequencing Trio<\/jats:italic>(<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.genedx.com\/test-catalog\/available-tests\/xomedx-whole-exome-sequencing-trio\/\">https:\/\/www.genedx.com\/test-catalog\/available-tests\/xomedx-whole-exome-sequencing-trio\/<\/jats:ext-link>). WES uses next\u2010generation sequencing (NGS) technology to assess for variants within the coding regions, or exons, of approximately 23,000 genes. For the<jats:italic>FLNB<\/jats:italic>gene (NM_001457.3), 100% of the coding region was covered at a minimum of 10x. GeneDx uses Sanger sequencing to confirm NGS variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>WES revealed a heterozygous pathogenic variant, p.Glu227Lys (c.679G&gt;A), in the<jats:italic>FLNB<\/jats:italic>gene in three out of the four family members tested. This variant is associated with Larsen syndrome, a skeletal dysplasia condition with a wide range of phenotypic variability that usually includes congenital joint dislocations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is a highly unusual presentation of Larsen syndrome in which the identifying hallmark trait is absent in the patients\u2019 phenotypes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.648","type":"journal-article","created":{"date-parts":[[2019,3,27]],"date-time":"2019-03-27T21:51:31Z","timestamp":1553723491000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A case study of atypical Larsen syndrome with absent hallmark joint dislocations"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8140-5373","authenticated-orcid":false,"given":"Neslida","family":"Kodra","sequence":"first","affiliation":[{"name":"Inova Translational Medicine Institute, Inova Fairfax Hospital Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Callie","family":"Diamonstein","sequence":"additional","affiliation":[{"name":"Inova Translational Medicine Institute, Inova Fairfax Hospital Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7663-1851","authenticated-orcid":false,"given":"Natalie S.","family":"Hauser","sequence":"additional","affiliation":[{"name":"Inova Translational Medicine Institute, Inova Fairfax Hospital Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,27]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.043687"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.60"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22012"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20348"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.05.006"},{"key":"e_1_2_5_7_1","first-page":"45","article-title":"The association of a hearing deficit with Larsen's syndrome","volume":"10","author":"Herrmann H. 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