{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T21:07:05Z","timestamp":1789679225041,"version":"4.0.1"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2012,7,27]],"date-time":"2012-07-27T00:00:00Z","timestamp":1343347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Noonan syndrome with multiple giant cell lesions (NS\/MGCL) was recently shown to be a phenotypic variation within the syndromes of the Ras\/MAPK pathway and not an independent entity as previously thought. Here we report on a 13\u2010year\u2010old boy with a typical phenotype of NS including atrial septal defect, pulmonic stenosis, short stature, and combined pectus carinatum\/excavatum, pronounced MGCL of both jaws, and a de novo mutation in <jats:italic>PTPN11<\/jats:italic>, c.236A&gt;G (which predicts p.Q79R). Mutations in <jats:italic>PTPN11<\/jats:italic> are the most frequent cause of NS and p.Q79R is a recurrent mutation in exon 3. Including this patient, 24 patients with molecularly confirmed NS, LEOPARD, or CFC\/MGCL syndrome have been reported to date, of these 21 patients have <jats:italic>PTPN11<\/jats:italic>, <jats:italic>SOS1<\/jats:italic>, or <jats:italic>RAF1<\/jats:italic> mutations and three have <jats:italic>BRAF<\/jats:italic> or <jats:italic>MAP2K1<\/jats:italic> mutations, confirming that MGCL is a rare complication of the deregulated RAS\/MAPK pathway. In all patients, the lesions of the mandible and to a lesser extent of the maxilla were first noted between ages 2 and 19 years (median 11 years), and were combined with enlargement of the jaws in 11\/24 patients (46%). In this case and, with one exception (mutation not reported), all previous cases the NS\/MGCL was caused by known mutations in the <jats:italic>PTPN11<\/jats:italic>, <jats:italic>SOS1<\/jats:italic>, <jats:italic>RAF1<\/jats:italic>, <jats:italic>BRAF1<\/jats:italic>, and <jats:italic>MAP2K1<\/jats:italic> genes that were previously reported with RASopathies without MGCL. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.35493","type":"journal-article","created":{"date-parts":[[2012,7,28]],"date-time":"2012-07-28T09:10:45Z","timestamp":1343466645000},"page":"2283-2289","source":"Crossref","is-referenced-by-count":25,"title":["Case report: Noonan syndrome with multiple giant cell lesions and review of the 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