{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T15:56:47Z","timestamp":1783612607139,"version":"3.55.0"},"reference-count":24,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T00:00:00Z","timestamp":1589241600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Noonan syndrome is an autosomal dominant disorder secondary to RASopathies, which are caused by germ\u2010line mutations in genes encoding components of the RAS mitogen\u2010activated protein kinase pathway. RIT1 (OMIM *609591) was recently reported as a disease gene for Noonan syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>We present a patient with <jats:italic>RIT1\u2010<\/jats:italic>associated Noonan syndrome, who in addition to the congenital heart defect, had monocytosis, myeloproliferative disorder, and accelerated idioventricular rhythm that was associated with severe hemodynamic instability. Noonan syndrome was suspected given the severe pulmonary stenosis, persistent monocytosis, and \u201cleft\u2010shifted\u201d complete blood counts without any evidence of an infectious process. Genetic testing revealed that the patient had a heterozygous c.221 C&gt;G (pAla74Gly) mutation in the <jats:italic>RIT1<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We report a case of neonatal Noonan syndrome associated with <jats:italic>RIT1<\/jats:italic> mutation. The clinical suspicion for Noonan syndrome was based only on the congenital heart defect, persistent monocytosis, and myeloproliferative process as the child lacked all other hallmarks characteristics of Noonan syndrome. However, the patient had an unusually malignant ventricular dysrhythmia that lead to his demise. The case highlights the fact that despite its heterogeneous presentation, <jats:italic>RIT1<\/jats:italic>\u2010associated Noonan syndrome can be extremely severe with poor outcome.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1253","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T18:02:03Z","timestamp":1589306523000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Complicated ventricular arrhythmia and hematologic myeloproliferative disorder in <i>RIT1\u2010<\/i>associated Noonan syndrome: Expanding the phenotype and review of the literature"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1823-453X","authenticated-orcid":false,"given":"Safwat A.","family":"Aly","sequence":"first","affiliation":[{"name":"Department of Pediatrics Rush University Medical College Chicago IL USA"},{"name":"Division of Cardiology Department of Pediatrics The Hospital for Sick Children University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth M.","family":"Boyer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Rush University Medical College Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brie\u2010Ann A.","family":"Muller","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Rush University Medical College Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Marini","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Pediatrics The Hospital for Sick Children University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn H.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Rush University Medical College Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoang H.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Rush University Medical College Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.05.021"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36722"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.137"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.273"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1324128111"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/ahg.12140"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-007-9024-z"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36646"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.97"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12608"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.581"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.32"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38854"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37657"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-015-2658-6"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpedi.1968.02100020377005"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2017.03.009"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61023-X"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1926"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2009-3207"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102611"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng772"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1156"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-015-1627-5"}],"container-title":["Molecular Genetics &amp; 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