{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T22:12:44Z","timestamp":1757628764180,"version":"3.44.0"},"reference-count":19,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Noonan syndrome is a genetic multisystem congenital disorder, caused by pathogenic variants in genes that encode components of the RAS\/MAPK signaling pathway. Pathogenic variants in <jats:italic>SOS2<\/jats:italic> represent less than 2% of cases with NS. The phenotype includes a particularly high prevalence (65%) of lymphatic disease. Recently, severe nerve enlargements were described in patients with a pathogenic variant in <jats:italic>SOS2<\/jats:italic>. To establish the occurrence of nerve enlargements in <jats:italic>SOS2<\/jats:italic>\u2010related Noonan syndrome, we retrospectively analyzed the data of all six patients with <jats:italic>SOS2<\/jats:italic>\u2010related Noonan syndrome at our center. All patients had undergone high\u2010resolution nerve ultrasound for clinical reasons, and all had enlarged nerves, most of them severe. All of our patients and the three patients with enlarged nerves described in three published case series have an amino acid substitution at p.Met267.<\/jats:p>","DOI":"10.1002\/ajmg.a.64142","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T03:33:28Z","timestamp":1749094408000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Severe Nerve Enlargement in <i>SOS2<\/i>\u2010Related Noonan Syndrome"],"prefix":"10.1002","volume":"197","author":[{"given":"Erika","family":"Leenders","sequence":"first","affiliation":[{"name":"Department of Human Genetics Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fieke","family":"Draaisma","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Radboud Institute for Health Sciences, Radboud University Medical Center Amalia Children's Hospital  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corrie E.","family":"Erasmus","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center Amalia Children's Hospital  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catelijne","family":"Coppens","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Radboud Institute for Health Sciences, Radboud University Medical Center Amalia Children's Hospital  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0553-7064","authenticated-orcid":false,"given":"Lotte E. 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