{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:11:22Z","timestamp":1790179882199,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2008,3,17]],"date-time":"2008-03-17T00:00:00Z","timestamp":1205712000000},"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":[[2008,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Noonan syndrome is an autosomal dominant disorder with an estimated incidence of 1 in 1,000 to 1 in 2,500 live births. It is characterized by postnatal\u2010onset short stature, characteristic facial changes, webbed neck, pectus carinatum, or excavatum, congenital heart defects, and bleeding abnormalities. Gain\u2010of\u2010function mutations in the <jats:italic>PTPN11<\/jats:italic>, <jats:italic>KRAS<\/jats:italic>, <jats:italic>SOS1<\/jats:italic>, and <jats:italic>RAF1<\/jats:italic> genes that are components of the RAS\/MEPK signaling pathway are identified in about 70\u201385% of individuals with Noonan syndrome. We report here a case of duplication of chromosome region 12q24.11q24.23 identified by array comparative genomic hybridization (aCGH) that includes the <jats:italic>PTPN11<\/jats:italic> gene in a 3\u2010year\u2010old girl with apparent Noonan syndrome. The patient presented with postnatal\u2010onset failure\u2010to\u2010thrive, developmental delay, microcephaly, velopalatal incompetence, pectus excavatum, coarctation of aorta, atrial and ventricular septal defects, decreased muscle tone, and minor facial anomalies consistent with Noonan syndrome. At 3 years of age her speech, gross and fine motor development were at the level of a 12\u201318 month old child. This degree of developmental delay was atypical for an individual with Noonan syndrome, raising concerns for a chromosomal abnormality. Array\u2010CGH showed an interstitial duplication of 10 Mb including the <jats:italic>PTPN11<\/jats:italic> gene. Sequencing of <jats:italic>PTPN11<\/jats:italic>, <jats:italic>KRAS<\/jats:italic>, <jats:italic>SOS1<\/jats:italic> and the coding region of <jats:italic>RAF1<\/jats:italic> did not identify mutations. The increased gene dosage of the <jats:italic>PTPN11<\/jats:italic> gene in the form of duplication is expected to have the same consequence as gain\u2010of\u2010function mutations seen in Noonan syndrome. We propose that at least some of the 15\u201330% of individuals with Noonan syndrome who do not have a mutation by sequencing may have a gain in copy number of <jats:italic>PTPN11<\/jats:italic> and recommend that comprehensive testing for Noonan syndrome should include analysis for copy number changes of <jats:italic>PTPN11<\/jats:italic>. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.32215","type":"journal-article","created":{"date-parts":[[2008,3,17]],"date-time":"2008-03-17T19:46:32Z","timestamp":1205783192000},"page":"1042-1048","source":"Crossref","is-referenced-by-count":39,"title":["Duplication of chromosome band 12q24.11q24.23 results in apparent Noonan syndrome"],"prefix":"10.1002","volume":"146A","author":[{"given":"Oleg A.","family":"Shchelochkov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankita","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George M.","family":"Weissenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Craig","family":"Chinault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Wiszniewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscilla H.","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Eng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary K.","family":"Kukolich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. 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