{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:48:04Z","timestamp":1790837284679,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:00:00Z","timestamp":1647907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Multiple synostoses syndromes (SYNS) are autosomal dominant syndromes characterized by multiple joint fusions commonly involving the carpal\u2010tarsal, interphalangeal, humeroradial, and cervical spine joints. They display genetic heterogeneity with pathogenic variants reported in four separate genes (<jats:italic>NOG, GDF5, FGF9<\/jats:italic>, and <jats:italic>GDF6<\/jats:italic>) defining four different SYNS forms. <jats:italic>FGF9<\/jats:italic> variants have been reported in SYNS3, a SYNS with multiple synostoses, normal cognition, normal hearing, and craniosynostosis. Here, we report a novel <jats:italic>FGF9<\/jats:italic> c.569G\u00a0&gt;\u00a0C p.(Arg190Thr) variant identified by whole\u2010exome sequencing in a patient with multiple bony abnormalities. The patient initially presented with elbow instability and decreased range of motion. Imaging revealed bilateral radial head deformities, carpal\u2010tarsal fusions, brachydactyly, and osteoarthritis of the sacroiliac joints. In silico protein modeling of the identified <jats:italic>FGF9<\/jats:italic> variant predicts decreased stability of ligand\u2010receptor binding supporting the pathogenicity of this finding. This finding expands the repertoire of <jats:italic>FGF9<\/jats:italic> variants and phenotypic information reported for SYNS3 and suggest that genotype phenotype correlations due to localization seem less likely and more so due to the consequence of the pathogenic variant on the receptor. This is useful in the counseling in families as more de novo variants emerge.<\/jats:p>","DOI":"10.1002\/ajmg.a.62729","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T11:49:11Z","timestamp":1647949751000},"page":"2162-2167","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Novel <scp>FGF9<\/scp> variant contributes to multiple synostoses syndrome 3"],"prefix":"10.1002","volume":"188","author":[{"given":"Stephanie M.","family":"Dobson","sequence":"first","affiliation":[{"name":"Queen's Medical School Queen's University  Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Kiss","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics Queen's University  Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Borschneck","sequence":"additional","affiliation":[{"name":"Department of Surgery Queen's University  Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen E.","family":"Heath","sequence":"additional","affiliation":[{"name":"Institute of Medical &amp; Molecular Genetics (INGEMM), Hospital Universitario La Paz, IdiPAZ Universidad de Madrid  Madrid Spain"},{"name":"Skeletal dysplasia multidisciplinary Unit and ERN\u2010BOND Hospital Universitario La Paz  Madrid Spain"},{"name":"CIBERER, ISCIII  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Gross","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Molecular Therapeutics, Department of Biochemistry and Molecular Biology, Chicago Medical School Rosalind Franklin University of Medicine and Science  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc J.","family":"Glucksman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2941-7603","authenticated-orcid":false,"given":"Andrea","family":"Guerin","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics Queen's University  Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1086\/503204"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2004.10.003"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/6821"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.316"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23912"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1086\/301921"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.74419"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2017.06.016"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2014.2998"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23292"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13876"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.2001.600607.x"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx029"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38503"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13880"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2016.12.005"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.13588"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2761"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01545"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.06.007"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62729","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62729","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62729","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T08:56:20Z","timestamp":1692867380000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62729"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,22]]},"references-count":21,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1002\/ajmg.a.62729"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62729","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,22]]},"assertion":[{"value":"2021-08-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}