{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T14:32:30Z","timestamp":1782743550745,"version":"3.54.5"},"reference-count":14,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","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":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Myhre syndrome is a rare disorder caused by pathogenic gain\u2010of\u2010function variants in the <jats:italic>SMAD4<\/jats:italic> gene. Most of the patients have had <jats:italic>de novo<\/jats:italic> variants. There are several instances of autosomal dominant inheritance, and penetrance appears to be complete. We describe seven Brazilian patients, three of whom are siblings carrying the recurrent c.1486C&gt;T p.(Arg496Cys) variant in <jats:italic>SMAD4<\/jats:italic> inherited from the father. The other three patients are unrelated simplex cases. All affected individuals have clinical features commonly found in Myhre syndrome, including typical dysmorphic facial features, with intra\u2010 and interfamilial clinical heterogeneity. Five of the patients have developmental delay and\/or clinical signs of intellectual disability. However, only one had neuropsychological testing. Only one patient had a diagnosis of autism spectrum disorder. As in previously reported families, this new family has the same c.1486C&gt;T p.(Arg496Cys) variant. This is the first study describing Brazilian patients with Myhre syndrome, highlighting the clinical variability of this rare disease. We reinforce the need to investigate the parents to provide appropriate genetic counseling.<\/jats:p>","DOI":"10.1002\/ajmg.a.63984","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T08:30:22Z","timestamp":1736929822000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<scp><i>SMAD4<\/i><\/scp> Pathogenic Variants in Seven New Brazilian Individuals With Myhre Syndrome Including a New Family"],"prefix":"10.1002","volume":"197","author":[{"given":"Samira","family":"Spineli\u2010Silva","sequence":"first","affiliation":[{"name":"Medical Genetics and Genomic Medicine\u2014Department of Translational Medicine School of Medical Sciences  Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa Bretanha","family":"Pontes","sequence":"additional","affiliation":[{"name":"Medical Genetics and Genomic Medicine\u2014Department of Translational Medicine School of Medical Sciences  Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"de Leeuw","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela Rold\u00e3o","family":"Correia\u2010Costa","sequence":"additional","affiliation":[{"name":"Medical Genetics and Genomic Medicine\u2014Department of Translational Medicine School of Medical Sciences  Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa Bittencourt","family":"de Wallau","sequence":"additional","affiliation":[{"name":"Medical Genetics and Genomic Medicine\u2014Department of Translational Medicine School of Medical Sciences  Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz Ribeiro","family":"Versiani","sequence":"additional","affiliation":[{"name":"University Hospital University of Brasilia  Brasilia Brazil"},{"name":"National Institute of Rare Diseases (InRaras Brazil) University of Brasilia  Brasilia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6161-0510","authenticated-orcid":false,"given":"Juliana Forte","family":"Mazzeu","sequence":"additional","affiliation":[{"name":"National Institute of Rare Diseases (InRaras Brazil) University of Brasilia  Brasilia Brazil"},{"name":"Faculty of Medicine University of Brasilia  Brasilia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Boy","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera L\u00facia","family":"Gil\u2010da\u2010Silva\u2010Lopes","sequence":"additional","affiliation":[{"name":"Medical Genetics and Genomic Medicine\u2014Department of Translational Medicine School of Medical Sciences  Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4027-8341","authenticated-orcid":false,"given":"T\u00e1rsis Paiva","family":"Vieira","sequence":"additional","affiliation":[{"name":"Medical Genetics and Genomic Medicine\u2014Department of Translational Medicine School of Medical Sciences  Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36544"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.12.011"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000527149"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1016"},{"key":"e_1_2_8_6_1","volume-title":"GeneReviews","author":"Lin A. 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