{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T20:11:54Z","timestamp":1784146314839,"version":"3.55.0"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,5,5]],"date-time":"2011-05-05T00:00:00Z","timestamp":1304553600000},"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":[[2011,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Noonan syndrome (NS) is a heterogeneous disorder caused by activating mutations in the RAS\u2010MAPK signaling pathway. It is associated with variable clinical expression including short stature, congenital heart defect, unusual pectus deformity, and typical facial features and the inheritance is autosomal dominant. Here, we present a clinical and molecular characterization of a patient with Noonan\u2010like syndrome with loose anagen hair phenotype and additional features including mild psychomotor developmental delay, osteoporosis, gingival hyperplasia, spinal neuroblastoma, intrathoracic extramedullary hematopoiesis, and liver hemangioma. Mutation analysis of <jats:italic>PTPN11<\/jats:italic>, <jats:italic>SOS1<\/jats:italic>, <jats:italic>RAF1<\/jats:italic>, <jats:italic>KRAS<\/jats:italic>, <jats:italic>BRAF<\/jats:italic>, <jats:italic>MEK1<\/jats:italic>, <jats:italic>MEK2<\/jats:italic>, <jats:italic>NRAS<\/jats:italic>, and <jats:italic>SHOC2<\/jats:italic> was conducted, revealing a co\u2010occurrence of two heterozygous previously identified mutations in the index patient. The mutation <jats:italic>SHOC2<\/jats:italic> c.4A\u2009&gt;\u2009G; p.Ser2Gly represents a de novo mutation, whereas, <jats:italic>PTPN11<\/jats:italic> c.1226G\u2009&gt;\u2009C; p.Gly409Ala was inherited from the mother and also identified in the brother. The mother and the brother present with some NS manifestations, such as short stature, delayed puberty, keratosis pilaris, caf\u00e9\u2010au\u2010lait spots, refraction error (mother), and undescended testis (brother), but no NS facial features, supporting the notion that the <jats:italic>PTPN11<\/jats:italic> p.Gly409Ala mutation leads to a relatively mild phenotype. We propose that, the atypical phenotype of the young woman with NS reported here is an additive effect, where the <jats:italic>PTPN11<\/jats:italic> mutation acts as a modifier. Interestingly, co\u2010occurrence of RAS\u2010MAPK mutations has been previously identified in a few patients with variable NS or neurofibromatosis\u2010NS phenotypes. Taken together, the results suggest that co\u2010occurrence of mutations or modifying loci in the RAS\u2010MAPK pathway may contribute to the clinical variability observed among NS patients. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.33987","type":"journal-article","created":{"date-parts":[[2011,5,5]],"date-time":"2011-05-05T16:55:41Z","timestamp":1304614541000},"page":"1217-1224","source":"Crossref","is-referenced-by-count":26,"title":["Co\u2010occurring <i>SHOC2<\/i> and <i>PTPN11<\/i> mutations in a patient with severe\/complex Noonan syndrome\u2010like phenotype"],"prefix":"10.1002","volume":"155","author":[{"given":"Sara","family":"Ekvall","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Hagen\u00e4s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Allanson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6ran","family":"Anner\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Louise","family":"Bondeson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,5,5]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.24.1.9"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-1923"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30813"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1089\/gtmb.2009.0192"},{"key":"e_1_2_5_6_1","doi-asserted-by":"crossref","first-page":"724279","DOI":"10.1155\/2010\/724279","article-title":"Paravertebral mass in a patient with hemolytic anemia:Computed tomographic findings","volume":"2010","author":"Carvalho JF","year":"2010","journal-title":"Case Rep Med"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-008-9126-y"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.497"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.425"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.055772"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-007-0558-0"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-10-250779"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10241"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2221"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.06.015"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.10923"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergencyto.2007.12.005"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.050450"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.057653"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2008.01170.x"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng2078"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20955"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2109"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32837"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2009.04.001"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-2-4"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2006.08.003"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.33987","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.33987","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T18:08:27Z","timestamp":1697652507000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.33987"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,5,5]]},"references-count":26,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2011,6]]}},"alternative-id":["10.1002\/ajmg.a.33987"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.33987","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,5,5]]}}}