{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T21:52:54Z","timestamp":1747173174565,"version":"3.40.5"},"reference-count":26,"publisher":"Wiley","license":[{"start":{"date-parts":[[2019,4,29]],"date-time":"2019-04-29T00:00:00Z","timestamp":1556496000000},"content-version":"unspecified","delay-in-days":118,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genet. Res."],"published-print":{"date-parts":[[2019]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Noonan syndrome and related disorders are a group of clinically and genetically heterogeneous conditions caused by mutations in genes of the RAS\/MAPK pathway. Noonan syndrome causes multiple congenital anomalies, which are frequently accompanied by hypertrophic cardiomyopathy (HCM). We report here a Tunisian patient with a severe phenotype of Noonan syndrome including neonatal HCM, facial dysmorphism, severe failure to thrive, cutaneous abnormalities, pectus excavatum and severe stunted growth, who died in her eighth month of life. Using whole exome sequencing, we identified a<jats:italic>de novo<\/jats:italic>mutation in exon 7 of the<jats:italic>RAF1<\/jats:italic>gene: c.776C &gt; A (p.Ser259Tyr). This mutation affects a highly conserved serine residue, a main mediator of Raf-1 inhibition via phosphorylation. To our knowledge the c.776C &gt; A mutation has been previously reported in only one case with prenatally diagnosed Noonan syndrome. Our study further supports the striking correlation of<jats:italic>RAF1<\/jats:italic>mutations with HCM and highlights the clinical severity of Noonan syndrome associated with a<jats:italic>RAF1<\/jats:italic>p.Ser259Tyr mutation.<\/jats:p>","DOI":"10.1017\/s0016672319000041","type":"journal-article","created":{"date-parts":[[2019,4,29]],"date-time":"2019-04-29T04:59:16Z","timestamp":1556513956000},"source":"Crossref","is-referenced-by-count":5,"title":["A severe clinical phenotype of Noonan syndrome with neonatal hypertrophic cardiomyopathy in the second case worldwide with<i>RAF1<\/i>S259Y neomutation"],"prefix":"10.1155","volume":"101","author":[{"given":"Hager","family":"Jaouadi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amel Ben","family":"Chehida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilia","family":"Kraoua","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather C.","family":"Etchevers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurent","family":"Argiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia","family":"Kasdallah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Blibech","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Val\u00e9rie","family":"Delague","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"L\u00e9vy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N\u00e9ji","family":"Tebib","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ridha","family":"Mrad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Abdelhak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rym","family":"Benkhalifa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0811-418X","authenticated-orcid":false,"given":"St\u00e9phane","family":"Zaffran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,4,29]]},"reference":[{"key":"S0016672319000041_ref26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2012.04.018"},{"key":"S0016672319000041_ref25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-200X.2009.03020.x"},{"key":"S0016672319000041_ref24","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0000000000000194"},{"key":"S0016672319000041_ref23","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2010.09.002"},{"key":"S0016672319000041_ref19","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2009.11.012"},{"key":"S0016672319000041_ref18","doi-asserted-by":"publisher","DOI":"10.1038\/ng2078"},{"key":"S0016672319000041_ref17","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2013-305047"},{"key":"S0016672319000041_ref16","doi-asserted-by":"publisher","DOI":"10.1038\/ng2073"},{"key":"S0016672319000041_ref15","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.057653"},{"key":"S0016672319000041_ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2011.05.024"},{"key":"S0016672319000041_ref9","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37024"},{"key":"S0016672319000041_ref10","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-008-0343-6"},{"key":"S0016672319000041_ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2003.09.031"},{"key":"S0016672319000041_ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2006.01.003"},{"key":"S0016672319000041_ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ppedcard.2015.01.002"},{"key":"S0016672319000041_ref12","first-page":"687","article-title":"Two cases of LEOPARD syndrome--RAF1 mutations firstly described in children","volume":"53","author":"Kuburovi\u0107","year":"2011","journal-title":"The Turkish Journal of Pediatrics"},{"key":"S0016672319000041_ref11","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21187"},{"key":"S0016672319000041_ref21","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36588"},{"key":"S0016672319000041_ref7","doi-asserted-by":"publisher","DOI":"10.1002\/pd.4797"},{"key":"S0016672319000041_ref22","unstructured":"Search by Disease. 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