{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T11:22:10Z","timestamp":1761218530262,"version":"3.40.5"},"reference-count":5,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,5]],"date-time":"2022-11-05T00:00:00Z","timestamp":1667606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Phenotype analysis of the Noonan syndrome (NS) related to <jats:italic>RAF1<\/jats:italic> mutations demonstrates that a high proportion of cases exhibit severe lymphatic dysplasia and congenital heart disease, especially hypertrophic cardiomyopathy. Because of the difficulty of fetal phenotypic assessment, the percentage of cases with multisystemic prenatal presentation as well as the phenotypic variability may be underestimated. We describe a 35\u2009weeks male preterm infant presenting with de novo missense mutation NM_002880.4(<jats:italic>RAF1<\/jats:italic>):c.770C&gt;T (p.Ser257Leu), whose death occurred following birth. Antenatal ultrasound showed polyhydramnios, severe ascites, and tongue protrusion. Autopsy revealed multiple congenital anomalies including intrauterine growth restriction, hydrops fetalis, characteristic facial dysmorphia, short and webbed neck, hypertrichosis, severe lungs hypoplasia, thymic hyperplasia, hepato\u2010splenomegaly, bilateral mild uretero\u2010hydronephrosis, and mild pontocerebellar hypoplasia. Histology revealed increased hepatic hematopoiesis and iron deposits. This report confirms that NS may be associated with multisystem involvement and provides further evidence for the wide phenotypic variability associated with <jats:italic>RAF1<\/jats:italic> variants.<\/jats:p>","DOI":"10.1002\/ajmg.a.63035","type":"journal-article","created":{"date-parts":[[2022,11,5]],"date-time":"2022-11-05T08:19:55Z","timestamp":1667636395000},"page":"630-633","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A severe clinicopathologic phenotype of <i>RAF1<\/i><scp>Ser257Leu<\/scp> neomutation in a preterm infant without cardiac anomaly"],"prefix":"10.1002","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-0011","authenticated-orcid":false,"given":"Sihem","family":"Darouich","sequence":"first","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine de Tunis Universit\u00e9 de Tunis El Manar  Tunis Tunisia"},{"name":"Unit\u00e9 de Pathologie Foetale et Placentaire, CHU Habib Bougatfa  Bizerte Tunisie"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed Sahbi","family":"Chakroun","sequence":"additional","affiliation":[{"name":"Laboratoire d'Epid\u00e9miologie Mol\u00e9culaire et Pathologie Exp\u00e9rimentale, Institut Pasteur de Tunis  Tunis Tunisie"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Houda","family":"Bellamine","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Cytologie et Anatomie Pathologiques H\u00f4pital Menzel Bourguiba  Menzel Bourguiba Tunisie"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ichrak","family":"Khamassi","sequence":"additional","affiliation":[{"name":"D\u00e9partement de N\u00e9onatologie et P\u00e9diatrie CHU Habib Bougatfa  Bizerte Tunisie"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,11,5]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_6_2_1","DOI":"10.1002\/pd.2782"},{"doi-asserted-by":"publisher","key":"e_1_2_6_3_1","DOI":"10.1080\/21678707.2020.1719827"},{"doi-asserted-by":"publisher","key":"e_1_2_6_4_1","DOI":"10.1186\/s13041-019-0517-5"},{"doi-asserted-by":"publisher","key":"e_1_2_6_5_1","DOI":"10.1159\/000276766"},{"doi-asserted-by":"publisher","key":"e_1_2_6_6_1","DOI":"10.1097\/MCD.0000000000000194"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63035","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.63035","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63035","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T11:44:49Z","timestamp":1692445489000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63035"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,5]]},"references-count":5,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["10.1002\/ajmg.a.63035"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63035","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"type":"print","value":"1552-4825"},{"type":"electronic","value":"1552-4833"}],"subject":[],"published":{"date-parts":[[2022,11,5]]},"assertion":[{"value":"2022-07-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}