{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:02:35Z","timestamp":1789642955226,"version":"4.0.0"},"reference-count":31,"publisher":"BMJ","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2008,8]]},"abstract":"<jats:sec>\n                  <jats:title>Background:<\/jats:title>\n                  <jats:p>Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFC) are related disorders associated with disrupted RAS\/RAF\/MEK\/ERK signalling. NS, characterised by facial dysmorphism, congenital heart defects and short stature, is caused by mutations in the genes <jats:italic>PTPN11, SOS1<\/jats:italic>, <jats:italic>KRAS<\/jats:italic> and <jats:italic>RAF1<\/jats:italic>. CFC is distinguished from NS by the presence of ectodermal abnormalities and more severe mental retardation in addition to the NS phenotype. The genetic aetiology of CFC was recently assigned to four genes: <jats:italic>BRAF, KRAS, MEK1<\/jats:italic> and <jats:italic>MEK2<\/jats:italic>.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods:<\/jats:title>\n                  <jats:p>A comprehensive mutation analysis of <jats:italic>BRAF, KRAS, MEK1<\/jats:italic>, <jats:italic>MEK2<\/jats:italic> and <jats:italic>SOS1<\/jats:italic> in 31 unrelated patients without mutations in <jats:italic>PTPN11<\/jats:italic> is presented<jats:italic>.<\/jats:italic>\n                  <\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>Mutations were identified in seven patients with CFC (two in <jats:italic>BRAF<\/jats:italic>, one in <jats:italic>KRAS,<\/jats:italic> one in <jats:italic>MEK1<\/jats:italic>, two in <jats:italic>MEK2<\/jats:italic> and one in <jats:italic>SOS1<\/jats:italic>). Two mutations were novel: <jats:italic>MEK1<\/jats:italic> E203Q and <jats:italic>MEK2<\/jats:italic> F57L. The <jats:italic>SOS1<\/jats:italic> E433K mutation, identified in a patient diagnosed with CFC, has previously been reported in patients with NS. In one patient with NS, we also identified a mutation, <jats:italic>BRAF<\/jats:italic> K499E, that has previously been reported in patients with CFC. We thus suggest involvement of <jats:italic>BRAF<\/jats:italic> in the pathogenesis of NS also.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions:<\/jats:title>\n                  <jats:p>Taken together, our results indicate that the molecular and clinical overlap between CFC and NS is more complex than previously suggested and that the syndromes might even represent allelic disorders. Furthermore, we suggest that the diagnosis should be refined to, for example, NS\u2013<jats:italic>PTPN11<\/jats:italic>-associated or CFC\u2013<jats:italic>BRAF<\/jats:italic>-associated syndromes after the genetic defect has been established, as this may affect the prognosis and treatment of the patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2008.057653","type":"journal-article","created":{"date-parts":[[2008,5,4]],"date-time":"2008-05-04T07:54:05Z","timestamp":1209887645000},"page":"500-506","source":"Crossref","is-referenced-by-count":82,"title":["Noonan and cardio-facio-cutaneous syndromes: two clinically and genetically overlapping disorders"],"prefix":"10.1136","volume":"45","author":[{"given":"A-M","family":"Nystr\u00f6m","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Ekvall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Berglund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Bj\u00f6rkqvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Braathen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Duchen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Enell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Holmberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U","family":"Holmlund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Olsson-Engman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Anner\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M-L","family":"Bondeson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2008,5,2]]},"reference":[{"key":"2025101713260344000_45.8.500.1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0306-283"},{"key":"2025101713260344000_45.8.500.2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1136\/jmg.24.1.9","article-title":"Noonan 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