{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T03:27:26Z","timestamp":1789442846786,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,5,15]],"date-time":"2009-05-15T00:00:00Z","timestamp":1242345600000},"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":[[2009,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neurofibromatosis\u2010Noonan syndrome (NFNS), an entity which combines both features of Noonan syndrome (NS) and neurofibromatosis type 1 (NF1), was etiologically unresolved until recent reports demonstrated <jats:italic>NF1<\/jats:italic> mutations in the majority of patients with NFNS. The phenotypic overlap was explained by the involvement of the Ras pathway in both disorders, and, accordingly, clustering of the <jats:italic>NF1<\/jats:italic> mutations in the GTPase\u2010activating protein (GAP) domain of neurofibromin was observed in individuals with NFNS. We report on an 18\u2010month\u2010old girl with typical findings suggestive of NS in combination with multiple caf\u00e9\u2010au\u2010lait spots and bilateral optic gliomas suggestive of NF1. The patient was found to carry a de novo <jats:italic>PTPN11<\/jats:italic> mutation p.T2I as well as the maternally inherited <jats:italic>NF1<\/jats:italic> mutation c.4661+1G&gt;C. Her otherwise healthy mother and brother, who also had the <jats:italic>NF1<\/jats:italic> mutation, showed few caf\u00e9\u2010au\u2010lait spots as the only sign of neurofibromatosis. Since our patient's unique <jats:italic>NF1<\/jats:italic> mutation results in skipping of exon 27a and thus involves the same region, Gap\u2010related domain, that had been shown to be associated with NFNS, her phenotype could have been misleadingly attributed to the <jats:italic>NF1<\/jats:italic> mutation only. Contrarily, absence of both cutaneous neurofibromas and NS features in her relatives with the same <jats:italic>NF1<\/jats:italic> mutation, suggests that the index patient's typical NFNS phenotype is caused by an additive effect of mutations in both <jats:italic>NF1<\/jats:italic> and <jats:italic>PTPN11<\/jats:italic>. In contrast to previous findings, we speculate that absence of cutaneous neurofibromas is not solely associated with the recurrent 3\u2010bp in\u2010frame deletion in exon 17. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.32837","type":"journal-article","created":{"date-parts":[[2009,5,16]],"date-time":"2009-05-16T00:15:38Z","timestamp":1242432938000},"page":"1263-1267","source":"Crossref","is-referenced-by-count":50,"title":["Independent <i>NF1<\/i> and <i>PTPN11<\/i> mutations in a family with neurofibromatosis\u2010Noonan syndrome"],"prefix":"10.1002","volume":"149A","author":[{"given":"Christian","family":"Thiel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Wilken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Zenker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinrich","family":"Sticht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raimund","family":"Fahsold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele\u2010Charlotte","family":"Gusek\u2010Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Rauch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,5,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.24.1.9"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30138"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320210307"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00019052-200404000-00004"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19961218)66:3<347::AID-AJMG20>3.0.CO;2-L"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20023"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30813"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1986.tb48061.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1996.tb04328.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(02)00015-1"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1086\/498454"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1086\/341528"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31156"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1086\/302809"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80938-1"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31547"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320210308"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-006-0135-4"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.8.571"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320210309"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1004(200006)15:6<541::AID-HUMU6>3.0.CO;2-N"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(03)00091-4"},{"key":"e_1_2_7_24_1","first-page":"172","article-title":"National Institutes of Health Consensus Development Conference Statement: Neurofibromatosis. 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