{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T17:19:01Z","timestamp":1781198341422,"version":"3.54.1"},"reference-count":17,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T00:00:00Z","timestamp":1622678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T00:00:00Z","timestamp":1622678400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["303375\/2019\u20101"],"award-info":[{"award-number":["303375\/2019\u20101"]}],"id":[{"id":"10.13039\/501100003593","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","award":["2013\/08028\u20101"],"award-info":[{"award-number":["2013\/08028\u20101"]}],"id":[{"id":"10.13039\/501100001807","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":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Noonan syndrome (NS) is a Mendelian phenotype, member of a group of disorders sharing neurocardiofaciocutaneous involvement, known as RASopathies, caused by germline variants in genes coding for components of the RAS\/MAPK signaling pathway. Recently, a novel gene of the RAS family (\n                    <jats:italic>MRAS<\/jats:italic>\n                    ) was reported to be associated with NS in five children, all of them presenting, among the cardinal features of NS, the same cardiac finding, hypertrophic cardiomyopathy (HCM). We report on a 2\u2010month\u2010old infant boy also presenting this cardiac anomaly that evolved to a fatal outcome after a surgical myectomy. In addition, a thick walled left ventricle apical aneurysm, rarely described in NS, was also disclosed. Next\u2010generation sequencing revealed a missense, previously reported variant in\n                    <jats:italic>MRAS<\/jats:italic>\n                    (p.Thr68Ile). This report reinforces the high frequency of HCM among individuals harboring\n                    <jats:italic>MRAS<\/jats:italic>\n                    variants, contrasting to the 20% overall prevalence of this cardiac anomaly in NS. Thus, these preliminary data suggest that variants in\n                    <jats:italic>MRAS<\/jats:italic>\n                    per se are high risk factors for the development of an early, severe HCM, mostly of them with left ventricle outflow tract obstruction, with poor prognosis. Because of the severity of the cardiac involvement, other clinical findings could not be addressed in detail. Therefore, long\u2010term follow\u2010up of these individuals and further descriptions are required to fully understand the complete phenotypic spectrum of NS associated with\n                    <jats:italic>MRAS<\/jats:italic>\n                    germline variants, including if these individuals present an increased risk for cancer.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.62376","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T05:43:31Z","timestamp":1622785411000},"page":"3099-3103","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Atypical, severe hypertrophic cardiomyopathy in a newborn presenting Noonan syndrome harboring a recurrent heterozygous\n                    <scp>\n                      <i>MRAS<\/i>\n                    <\/scp>\n                    variant"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8649-976X","authenticated-orcid":false,"given":"Lucas Vieira Lacerda","family":"Pires","sequence":"first","affiliation":[{"name":"Unidade de Gen\u00e9tica, Instituto da Crian\u00e7a do Hospital das Cl\u00ednicas da Faculdade de Medicina Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata de Almeida","family":"Bordim","sequence":"additional","affiliation":[{"name":"Unidade de Cardiopatias Cong\u00eanitas, Instituto do Cora\u00e7\u00e3o do Hospital das Cl\u00ednicas da Faculdade de Medicina Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Beatriz Rabelo","family":"Maciel","sequence":"additional","affiliation":[{"name":"Unidade de Cardiopatias Cong\u00eanitas, Instituto do Cora\u00e7\u00e3o do Hospital das Cl\u00ednicas da Faculdade de Medicina Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Cristina Sayuri","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Unidade de Cardiopatias Cong\u00eanitas, Instituto do Cora\u00e7\u00e3o do Hospital das Cl\u00ednicas da Faculdade de Medicina Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme Lopes","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica, Instituto da Crian\u00e7a do Hospital das Cl\u00ednicas da Faculdade de Medicina Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"},{"name":"Instituto de Bioci\u00eancias Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"},{"name":"GeneOne, DASA  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9223-7341","authenticated-orcid":false,"given":"Rachel Sayuri","family":"Honjo","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica, Instituto da Crian\u00e7a do Hospital das Cl\u00ednicas da Faculdade de Medicina Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong Ae","family":"Kim","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica, Instituto da Crian\u00e7a do Hospital das Cl\u00ednicas da Faculdade de Medicina Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4701-6777","authenticated-orcid":false,"given":"Debora Romeo","family":"Bertola","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica, Instituto da Crian\u00e7a do Hospital das Cl\u00ednicas da Faculdade de Medicina Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"},{"name":"Instituto de Bioci\u00eancias Universidade de S\u00e3o Paulo  S\u00e3o 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