{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:01:22Z","timestamp":1792047682724,"version":"4.4.0"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,9,21]],"date-time":"2004-09-21T00:00:00Z","timestamp":1095724800000},"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":[[2004,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Noonan syndrome (NS) is an autosomal dominant disorder comprising short stature, facial dysmorphism, short and\/or webbed neck, heart defects, and cryptorchidism in males. The gene responsible for the disorder (<jats:italic>PTPN11<\/jats:italic>) was recently identified, and explains 30\u201350% of the cases clinically diagnosed as NS. Cardiofaciocutaneous (CFC) syndrome, a similar but distinct entity, is characterized by relative macrocephaly, characteristic facial appearance, ectodermal abnormalities (sparse and friable hair, sparse eyebrows, hyperkeratotic skin), congenital heart defects, and growth and mental retardation. We describe on a young woman who presents clinical features of NS (short stature, triangular facies, with dowslanting palpebral fissures and apparent hypertelorism, webbed neck, pulmonary stenosis, bleeding diathesis, prominent corneal nerves), but with a more prominent ectodermal involvement (sparse and very coarse hair, sparse eyebrows and eyelashes) and developmental delay\/mental retardation, which are characteristic of CFC patients. Sequencing of the <jats:italic>PTPN11<\/jats:italic> gene showed a T411M substitution, not previously described in patients with NS. The same mutation was found in her mother and older sister, not initially considered to be affected by NS, but with very subtle clinical findings compatible with this diagnosis. Molecular dynamic studies indicate that this new mutation, similar to other previously described mutations, favors a more active protein conformation. However, the main disruptive effect is not directly in the catalytic domain, suggesting that the location of this mutation could make the protein more susceptible to gene\u2013gene or gene\u2013environment interactions. Atypical cases of NS should be screened for mutations in the <jats:italic>PTPN11<\/jats:italic> gene and in the case of a positive result, first\u2010degree relatives should also be tested for the specific mutation. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.30270","type":"journal-article","created":{"date-parts":[[2004,9,21]],"date-time":"2004-09-21T23:19:41Z","timestamp":1095808781000},"page":"378-383","source":"Crossref","is-referenced-by-count":33,"title":["Clinical variability in a Noonan syndrome family with a new <i>PTPN11<\/i> gene mutation"],"prefix":"10.1002","volume":"130A","author":[{"given":"D\u00e9bora Romeo","family":"Bertola","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre C.","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo S.L. 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