{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T20:47:44Z","timestamp":1778532464589,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,6,6]],"date-time":"2005-06-06T00:00:00Z","timestamp":1118016000000},"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":[[2005,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>PTPN11<\/jats:italic> missense mutations cause approximately 50% of Noonan syndrome, an autosomal dominant disorder presenting with various congenital heart defects, most commonly valvar pulmonary stenosis, and hypertrophic cardiomyopathy. Atrioventricular septal defects and coarctation of the aorta occur in 15% and 9%, respectively. The aim of this study was to determine if <jats:italic>PTPN11<\/jats:italic> mutations exist in non\u2010syndromic patients with these two relevant forms of congenital heart disease. The 15 coding <jats:italic>PTPN11<\/jats:italic> exons and their intron boundaries from subjects with atrioventricular septal defects (n\u2009=\u200924) and coarctation of the aorta (n\u2009=\u2009157) were analyzed using denaturing high performance liquid chromatography and sequenced if abnormal. One subject with an atrioventricular septal defect but no other known medical problems had a c.127C\u2009&gt;\u2009T transition in exon 2, predicting a p.L43F substitution. This mutation affected the phosphotyrosine\u2010binding region in the N\u2010terminal src homology 2 domain and was close to a Noonan syndrome mutation (p.T42A). An otherwise healthy patient with aortic coarctation had a silent c.540C\u2009&gt;\u2009T change in exon 5 corresponding to p.D180D. Our study showed that <jats:italic>PTPN11<\/jats:italic> mutations are rarely found in two isolated forms of congenital heart disease that commonly occur in Noonan syndrome. The p.L43F mutation belongs to a rare class of <jats:italic>PTPN11<\/jats:italic> mutations altering the phosphotyrosine\u2010binding region. These mutations are not predicted to alter the autoinhibition of the <jats:italic>PTPN11<\/jats:italic> protein product, SHP\u20102, which is the mechanism for the vast majority of mutations causing Noonan syndrome. Future studies will be directed towards understanding these rare phosphotyrosine binding region mutants. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.30789","type":"journal-article","created":{"date-parts":[[2005,6,6]],"date-time":"2005-06-06T21:17:25Z","timestamp":1118092645000},"page":"146-151","source":"Crossref","is-referenced-by-count":26,"title":["<i>PTPN11<\/i> mutations play a minor role in isolated congenital heart disease"],"prefix":"10.1002","volume":"136A","author":[{"given":"Constance G.","family":"Weismann","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Hager","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Kaemmerer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. 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