{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:08:02Z","timestamp":1774645682733,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100013117","name":"International Fibrodysplasia Ossificans Progressiva Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013117","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016787","name":"Penn Center for Musculoskeletal Disorders","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013182","name":"Weldon FOP Research Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013182","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000871","name":"Mayo Clinic","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013182","name":"Weldon FOP Research Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013182","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":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Genetic variants are vital in informing clinical phenotypes, aiding physical diagnosis, guiding genetic counseling, understanding the molecular basis of disease, and potentially stimulating drug development. Here we describe two families with an ultrarare <jats:italic>ACVR1<\/jats:italic> gain\u2010of\u2010function pathogenic variant (codon 375, Arginine\u2009&gt;\u2009Proline; <jats:italic>ACVR1<\/jats:italic><jats:sup><jats:italic>R375P<\/jats:italic><\/jats:sup>) responsible for a mild nonclassic fibrodysplasia ossificans progressiva (FOP) phenotype. Both families include people with the ultrarare <jats:italic>ACVR1<\/jats:italic><jats:sup><jats:italic>R375P<\/jats:italic><\/jats:sup> variant who exhibit features of FOP while other individuals currently do not express any clinical signs of FOP. Thus, the mild <jats:italic>ACVR1<\/jats:italic><jats:sup><jats:italic>R375P<\/jats:italic><\/jats:sup> variant greatly expands the scope and understanding of this rare disorder.<\/jats:p>","DOI":"10.1002\/ajmg.a.62585","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T12:53:32Z","timestamp":1638449612000},"page":"806-817","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["An <scp><i>ACVR1<\/i><sup><i>R375P<\/i><\/sup><\/scp> pathogenic variant in two families with mild fibrodysplasia ossificans progressiva"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1277-5420","authenticated-orcid":false,"given":"Frederick S.","family":"Kaplan","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery The Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Medicine The Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"The Center for Research in FOP &amp; Related Disorders The Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay C.","family":"Groppe","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Texas A&amp;M University College of Dentistry  Dallas Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meiqi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery The Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"The Center for Research in FOP &amp; Related Disorders The Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8318-3943","authenticated-orcid":false,"given":"O. Will","family":"Towler","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery The Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"The Center for Research in FOP &amp; Related Disorders The Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Grunvald","sequence":"additional","affiliation":[{"name":"Division of General Internal Medicine, The Department of Medicine The University of California San Diego  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth","family":"Kalunian","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Immunology, The Department of Medicine UC San Diego School of Medicine  La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Staci","family":"Kallish","sequence":"additional","affiliation":[{"name":"The Center for Research in FOP &amp; Related Disorders The Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Division of Translational Medicine and Human Genetics The Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona","family":"Al Mukaddam","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery The Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Medicine The Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"The Center for Research in FOP &amp; Related Disorders The Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Pignolo","sequence":"additional","affiliation":[{"name":"The Department of Medicine, The Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eileen M.","family":"Shore","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery The Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"The Center for Research in FOP &amp; Related Disorders The Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Genetics The Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.53761"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01595-12"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.365932"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/17460441.2019.1660641"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/BLO.0b013e318126c049"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aac4358"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2017.10.027"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1385\/BMM:3:3-4:205"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1510540112"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000365770"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)80555-3"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1097-2765(01)00332-x"},{"key":"e_1_2_9_14_1","first-page":"1","article-title":"The medical management of fibrodysplasia ossificans progressiva: Current treatment considerations","volume":"2","author":"Kaplan F. S.","year":"2021","journal-title":"Proceedings of International Clinical Council on FOP"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2017.04.015"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37205"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20868"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-02872-2"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2018.03.027"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2018.01.002"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2728"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678707.2020.1751122"},{"issue":"2","key":"e_1_2_9_23_1","first-page":"437","article-title":"Fibrodysplasia ossificans progressiva: Diagnosis, management, and therapeutic horizons","volume":"10","author":"Pignolo R. J.","year":"2013","journal-title":"Pediatric Endocrinology Reviews"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020106317"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1783"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.612853"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2019.115116"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1473"}],"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.62585","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62585","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62585","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T00:01:56Z","timestamp":1692576116000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62585"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,2]]},"references-count":27,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1002\/ajmg.a.62585"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62585","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,2]]},"assertion":[{"value":"2021-06-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}