{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:08:07Z","timestamp":1774645687206,"version":"3.50.1"},"reference-count":26,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T00:00:00Z","timestamp":1628035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Fibrodysplasia Ossificans Progressiva (FOP) is a rare autosomal dominant disease characterized by congenital malformation of the great toes and progressive heterotopic ossification of soft tissues leading to cumulative disability. The genetic cause of FOP are mutations in the<jats:italic>ACVR1<\/jats:italic>gene that encodes a type I receptor of Bone Morphogenetic Proteins. The most recurrent mutation in FOP patients is R206H affecting the Glycine\u2010Serine rich domain and causing the hyper\u2010activation of the receptor and the responsivity to the non\u2010canonical ligand, Activin A.<\/jats:p><jats:p>In the present study, we described a 3\u2010years old child with early and highly suggestive clinical features of FOP who was found negative for the recurrent p.R206H substitution.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Molecular screening of the whole<jats:italic>ACVR1<\/jats:italic>coding sequence and functional characterization in transfection\u2010based assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and Conclusions<\/jats:title><jats:p>We identified a novel,<jats:italic>de novo<\/jats:italic>variant in the fifth<jats:italic>ACVR1<\/jats:italic>coding exon (NM_001111067.4:c.772A&gt;T; NP_001104537.1:p.(R258W)). This substitution, never reported in association with FOP, affects a conserved arginine residue in the kinase domain of the protein.<jats:italic>In silico<\/jats:italic>analysis predicted the pathogenicity of this substitution, demonstrated by<jats:italic>in vitro<\/jats:italic>assays showing that the p.R258W ACVR1 mutated receptor acquires the ability to transduce the aberrant Activin A\u2010mediated signaling, as observed for the gene variants associated with FOP.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1774","type":"journal-article","created":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T12:42:21Z","timestamp":1628080941000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A case of Fibrodysplasia Ossificans Progressiva associated with a novel variant of the<i>ACVR1<\/i>gene"],"prefix":"10.1002","volume":"9","author":[{"given":"Serena","family":"Cappato","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Sciences (DINOGMI) University of Genoa Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rasa","family":"Traberg","sequence":"additional","affiliation":[{"name":"Department of Genetics and Molecular Medicine Medical Academy Lithuanian University of Health Sciences Kaunas Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jolita","family":"Gintautiene","sequence":"additional","affiliation":[{"name":"Department of Paediatric Surgery Medical Academy Lithuanian University of Health Sciences Kaunas Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Zara","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, 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