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We report in details of the neonatal course, molecular analysis and 180-days of age follow-up in affected individuals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The early clinical spectrum included various types of CHDs, less noticeable multiple extracardiac anomalies and unspecific symptoms like poor feeding. Of the 8 variants identified from 6 genes, 2 in<jats:italic>RASA1<\/jats:italic>were novel: (NM_002890.2: c.2828\u00a0T\u2009&gt;\u2009C (p.Leu943Pro)) and (NM_002890.2: c.2001del (p.Pro668Leufs*10)), which functionally impaired the protein structure. There was a relatively high mortality rate of 33.33% (3\/9) for all the defects combined. A<jats:italic>RAF1<\/jats:italic>-deficient male and a<jats:italic>RASA1<\/jats:italic>-deficient male survived from severe heart failure by surgical interventions in early life.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results revealed that family-based ES was useful in identifying DNMs and causal genes for sporadic diseases and screening Rasopathies shortly after birth. We recommended a family-based ES and a full phenotypic evaluation including echocardiogram, magnetic resonance imaging, ultrasonography and coagulation screening in neonates with CHDs and a suspected genetic etiology.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12920-022-01336-3","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T04:02:54Z","timestamp":1661313774000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["RASopathies due to de novo pathogenic variants: clinical features, genetic findings and outcomes in nine neonates born with congenital heart defects"],"prefix":"10.1186","volume":"15","author":[{"given":"Simin","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanyang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianwen","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,24]]},"reference":[{"issue":"21","key":"1336_CR1","doi-asserted-by":"publisher","first-page":"2241","DOI":"10.1016\/j.jacc.2011.08.025","volume":"58","author":"D van der Linde","year":"2011","unstructured":"van der Linde D, Konings EE, Slager MA, Witsenburg M, Helbing WA, Takkenberg JJ, et al. 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Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine approved this study with a waiver of informed consent due to the nature of the study (Approval number: XHEC-D-2022-077).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declares that they have no competing interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"184"}}