{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:03:46Z","timestamp":1791295426097,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2014,4,8]],"date-time":"2014-04-08T00:00:00Z","timestamp":1396915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Istituto Superiore di Sanit\u00e0-Ricerca Corrente 2013"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:sec><jats:label\/><jats:p>Myhre syndrome (MYHRS, OMIM 139210) is an autosomal dominant disorder characterized by developmental and growth delay, athletic muscular built, variable cognitive deficits, skeletal anomalies, stiffness of joints, distinctive facial gestalt and deafness. Recently, <jats:italic>SMAD4<\/jats:italic> (OMIM 600993) was identified by exome sequencing as the disease gene mutated in MYHRS. Previously only three missense mutations affecting Ile<jats:sup>500<\/jats:sup> (p.Ile500Thr, p.Ile500Val, and p.Ile500Met) have been described in 22 unrelated subjects with MYHRS or a clinically related phenotype. Here we report on a 15\u2010year\u2010old boy with typical MYHRS and a novel heterozygous <jats:italic>SMAD4<\/jats:italic> missense mutation affecting residue Arg<jats:sup>496<\/jats:sup>. This finding provides further information about the distinctive <jats:italic>SMAD4<\/jats:italic> mutation spectrum in MYHRS. In silico structural analyses exploring the impact of the Arg\u2010to\u2010Cys change at codon 496 suggested that conformational changes promoted by replacement of Arg<jats:sup>496<\/jats:sup> impact the stability of the SMAD heterotrimer and\/or proper SMAD4 ubiquitination. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36544","type":"journal-article","created":{"date-parts":[[2014,4,8]],"date-time":"2014-04-08T21:51:03Z","timestamp":1396993863000},"page":"1835-1840","source":"Crossref","is-referenced-by-count":45,"title":["Novel <i>SMAD4<\/i> mutation causing Myhre syndrome"],"prefix":"10.1002","volume":"164","author":[{"given":"Viviana","family":"Caputo","sequence":"first","affiliation":[{"name":"Dipartimento di Medicina Sperimentale Sapienza Universit\u00e0 di Roma Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianfranco","family":"Bocchinfuso","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Chimiche Universit\u00e0 di Roma \u201cTor Vergata\u201d Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Castori","sequence":"additional","affiliation":[{"name":"Genetica Medica, Dipartimento di Medicina Molecolare Sapienza Universit\u00e0 di Roma, Azienda Ospedaliera S. Camillo Forlanini Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Traversa","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare Sapienza Universit\u00e0 di Roma Rome Italy"},{"name":"Dipartimento di Ematologia Oncologia e Medicina Molecolare, Istituto Superiore di Sanit\u00e0 Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Pizzuti","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale Sapienza Universit\u00e0 di Roma Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Stella","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Chimiche Universit\u00e0 di Roma \u201cTor Vergata\u201d Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Grammatico","sequence":"additional","affiliation":[{"name":"Genetica Medica, Dipartimento di Medicina Molecolare Sapienza Universit\u00e0 di Roma, Azienda Ospedaliera S. Camillo Forlanini Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8200-1733","authenticated-orcid":false,"given":"Marco","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Dipartimento di Ematologia Oncologia e Medicina Molecolare, Istituto Superiore di Sanit\u00e0 Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,4,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti770"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35440"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2003411"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.4462"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.12.011"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/84995"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2004.07.016"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)42026-1"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/425231"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.10.051"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20289"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-2706"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)15732-2"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5366.1086"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.06472"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207219"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208603"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.199"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.05.012"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1016"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35374"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3000488"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja0646491"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1350705"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1981.tb01798.x"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00421-X"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.36544","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.36544","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.36544","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T23:33:32Z","timestamp":1696548812000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.36544"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,4,8]]},"references-count":26,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2014,7]]}},"alternative-id":["10.1002\/ajmg.a.36544"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.36544","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,4,8]]}}}