{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T07:59:11Z","timestamp":1772611151479,"version":"3.50.1"},"reference-count":15,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T00:00:00Z","timestamp":1599609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100010135","name":"Finska L\u00e4kares\u00e4llskapet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010135","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The multiple pterygium syndromes (MPS) are rare disorders with disease severity ranging from lethal to milder forms. The nonlethal Escobar variant MPS (EVMPS) is characterized by multiple pterygia and arthrogryposis, as well as various additional features including congenital anomalies. The genetic etiology of EVMPS is heterogeneous and the diagnosis has been based either on the detection of pathogenic <jats:italic>CHRNG<\/jats:italic> variants (~23% of patients), or suggestive clinical features. We describe four patients with a clinical suspicion of EVMPS who manifested with multiple pterygia, mild flexion contractures of several joints, and vertebral anomalies. We revealed recessively inherited <jats:italic>MYH3<\/jats:italic> variants as the underlying cause in all patients: two novel variants, c.1053C&gt;G, p.(Tyr351Ter) and c.3102+5G&gt;C, as compound heterozygous with the hypomorphic <jats:italic>MYH3<\/jats:italic> variant c.\u20109+1G&gt;A. Recessive <jats:italic>MYH3<\/jats:italic> variants have been previously associated with spondylocarpotarsal synostosis syndrome. Our findings now highlight multiple pterygia as an important feature in patients with recessive <jats:italic>MYH3<\/jats:italic> variants. Based on all patients with recessive <jats:italic>MYH3<\/jats:italic> variants reported up to date, we consider that this disease entity should be designated as \u201cContractures, pterygia, and variable skeletal fusions syndrome 1B,\u201d as recently suggested by OMIM. Our findings underline the importance of analyzing <jats:italic>MYH3<\/jats:italic> in the differential diagnosis of EVMPS, particularly as the hypomorphic <jats:italic>MYH3<\/jats:italic> variant might remain undetected by routine exome sequencing.<\/jats:p>","DOI":"10.1002\/ajmg.a.61836","type":"journal-article","created":{"date-parts":[[2020,9,27]],"date-time":"2020-09-27T09:14:03Z","timestamp":1601198043000},"page":"2605-2610","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Recessive <scp><i>MYH3<\/i><\/scp> variants cause \u201cContractures, pterygia, and variable skeletal fusions syndrome <scp>1B<\/scp>\u201d mimicking Escobar variant multiple pterygium syndrome"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7533-7124","authenticated-orcid":false,"given":"Anna H.","family":"Hakonen","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics, HUSLAB, HUS Diagnostic Center University of Helsinki and Helsinki University Hospital  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna","family":"Lehtonen","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland, FIMM, University of Helsinki  Helsinki Finland"},{"name":"Folkh\u00e4lsan Research Center  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sirpa","family":"Kivirikko","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, HUSLAB, HUS Diagnostic Center University of Helsinki and Helsinki University Hospital  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riikka","family":"Keski\u2010Filppula","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Oulu University Hospital, Medical Research Center Oulu and PEDEGO Research Unit, University of Oulu  Oulu Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jukka","family":"Moilanen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Oulu University Hospital, Medical Research Center Oulu and PEDEGO Research Unit, University of Oulu  Oulu Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reetta","family":"Kivisaari","sequence":"additional","affiliation":[{"name":"HUS Medical Imaging Center, Children's Hospital University of Helsinki and Helsinki University Hospital  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrikki","family":"Almusa","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland, FIMM, University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eveliina","family":"Jakkula","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, HUSLAB, HUS Diagnostic Center University of Helsinki and Helsinki University Hospital  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janna","family":"Saarela","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland, FIMM, University of Helsinki  Helsinki Finland"},{"name":"Centre for Molecular Medicine Norway (NCMM) University of Oslo  Oslo Norway"},{"name":"HUSLAB, HUS Diagnostic Center University of Helsinki and Helsinki University Hospital  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristiina","family":"Avela","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, HUSLAB, HUS Diagnostic Center University of Helsinki and Helsinki University Hospital  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristiina","family":"Aittom\u00e4ki","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, HUSLAB, HUS Diagnostic Center University of Helsinki and Helsinki University Hospital  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19961111)65:4<277::AID-AJMG6>3.0.CO;2-M"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.04.008"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2016.84"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61122"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.04.004"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1975"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/506257"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.08.016"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv216"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1086\/506256"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0075-8"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1775"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100378"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.231902.117"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep41803"}],"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.61836","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.61836","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.61836","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T05:55:23Z","timestamp":1693720523000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.61836"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,9]]},"references-count":15,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1002\/ajmg.a.61836"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.61836","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,9]]},"assertion":[{"value":"2020-02-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}