{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:15:49Z","timestamp":1788282949096,"version":"build-2803163510"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,12,24]],"date-time":"2020-12-24T00:00:00Z","timestamp":1608768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["GSP15001"],"award-info":[{"award-number":["GSP15001"]}],"id":[{"id":"10.13039\/501100002426","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":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Myhre syndrome (MS) is an ultra\u2010rare disorder due to pathogenic variants in the <jats:italic>SMAD4<\/jats:italic> gene that encodes a protein regulating the TGF\u2010\u03b2 pathway and extra\u2010cellular matrix (ECM) homeostasis. Main clinical features of MS include thickening of skin and joint stiffness. Previous studies showed that losartan improved ECM deposition in MS fibroblasts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Four molecularly confirmed MS subjects (mean age 23.8\u2009\u00b1\u200917\u2009years) were evaluated for: (a) skin thickness by Rodnan score, (b) joint range of motion (ROM) by goniometry, and (c) speckle\u2010tracking echocardiogram. Following baseline evaluations, three MS individuals received losartan for 12\u2009months and pre\u2010defined endpoints were monitored after 6 and 12\u2009months of treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At baseline, Rodnan scores were increased, joint ROM was reduced, and speckle\u2010tracking echocardiogram revealed reduced myocardial strain. In three MS subjects, improvements in skin thickness, joint ROM and to a lesser extent of myocardial strain, were observed after 6 and 12\u2009months of losartan treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although further long\u2010term controlled clinical trials with a larger number of affected individuals are needed, the present study suggests that losartan might improve skin, joint and heart abnormalities of MS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.62019","type":"journal-article","created":{"date-parts":[[2020,12,25]],"date-time":"2020-12-25T08:53:24Z","timestamp":1608886404000},"page":"702-709","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A pilot clinical trial with losartan in Myhre syndrome"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3934-2342","authenticated-orcid":false,"given":"Gerarda","family":"Cappuccio","sequence":"first","affiliation":[{"name":"Department of Translational Medicine Section of Pediatrics, Federico II University  Naples Italy"},{"name":"Telethon Institute of Genetics and Medicine  Pozzuoli (Naples) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Caiazza","sequence":"additional","affiliation":[{"name":"Inherited and Rare Disease Unit, AORN Colli, Department of Translational Medical Sciences 'Luigi Vanvitelli' University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Roca","sequence":"additional","affiliation":[{"name":"Department of Neurosciences and Reproductive and Odontostomatological Sciences Federico II University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Melis","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine Section of Pediatrics, Federico II University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Iuliano","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine  Pozzuoli (Naples) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabor","family":"Matyas","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Genetics and Gene Diagnostics, Foundation for People with Rare Diseases  Schlieren\u2010Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Rubino","sequence":"additional","affiliation":[{"name":"Inherited and Rare Disease Unit, AORN Colli, Department of Translational Medical Sciences 'Luigi Vanvitelli' University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8291-9517","authenticated-orcid":false,"given":"Giuseppe","family":"Limongelli","sequence":"additional","affiliation":[{"name":"Inherited and Rare Disease Unit, AORN Colli, Department of Translational Medical Sciences 'Luigi Vanvitelli' University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6895-8819","authenticated-orcid":false,"given":"Nicola","family":"Brunetti\u2010Pierri","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine Section of Pediatrics, Federico II University  Naples Italy"},{"name":"Telethon Institute of Genetics and Medicine  Pozzuoli (Naples) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38560"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201905-0922IM"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204309"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/echo.13547"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.12.011"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1124287"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kev201"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12969-020-00466-1"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2005.050187"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.5301\/jsrd.5000231"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12365"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1016"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2015.11.016"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37739"},{"key":"e_1_2_9_16_1","volume-title":"Kinesiology: scientific and, basis of human motion","author":"Luttgens K.","year":"1997"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10554-016-0838-8"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2013.283"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1053\/sarh.2001.20268"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3109\/14397595.2013.874749"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-7120-12-13"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8175.2011.01417.x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1517"}],"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.62019","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62019","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T07:38:59Z","timestamp":1693640339000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,24]]},"references-count":22,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["10.1002\/ajmg.a.62019"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62019","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,24]]},"assertion":[{"value":"2020-07-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}