{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T18:25:28Z","timestamp":1777659928217,"version":"3.51.4"},"reference-count":53,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2010,6,1]],"date-time":"2010-06-01T00:00:00Z","timestamp":1275350400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genetic Testing and Molecular Biomarkers"],"published-print":{"date-parts":[[2010,6,1]]},"abstract":"<jats:p>\n                    Noonan and Noonan-like syndromes are disorders of dysregulation of the rat sarcoma viral oncogene homolog (RAS)-mitogen-activated protein kinase signaling pathway. In Noonan syndrome (NS), four genes of this pathway (\n                    <jats:italic toggle=\"yes\">PTPN11<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">SOS1<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">RAF1<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">KRAS<\/jats:italic>\n                    ) are responsible for roughly 70% of the cases. We analyzed\n                    <jats:italic toggle=\"yes\">PTPN11<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">KRAS<\/jats:italic>\n                    genes by bidirectional sequencing in 95 probands with NS and 29 with Noonan-like syndromes, including previously reported patients already screened for\n                    <jats:italic toggle=\"yes\">PTPN11<\/jats:italic>\n                    gene mutations. In the new patients with NS, 20\/46 (43%) showed a\n                    <jats:italic toggle=\"yes\">PTPN11<\/jats:italic>\n                    gene mutation, two of them novel. In our total cohort, patients with NS and a\n                    <jats:italic toggle=\"yes\">PTPN11<\/jats:italic>\n                    mutation presented significantly higher prevalence of short stature (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.03) and pulmonary valve stenosis (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.01), and lower prevalence of hypertrophic cardiomyopathy (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.01). Only a single gene alteration, of uncertain role, was found in the\n                    <jats:italic toggle=\"yes\">KRAS<\/jats:italic>\n                    gene in an NS patient also presenting a\n                    <jats:italic toggle=\"yes\">PTPN11<\/jats:italic>\n                    gene mutation. We further analyzed the influence in clinical variability of three frequent polymorphisms found in the\n                    <jats:italic toggle=\"yes\">KRAS<\/jats:italic>\n                    gene and no statistically significant difference was observed among the frequency of clinical findings regarding the studied polymorphisms.\n                  <\/jats:p>","DOI":"10.1089\/gtmb.2009.0192","type":"journal-article","created":{"date-parts":[[2010,6,26]],"date-time":"2010-06-26T15:04:05Z","timestamp":1277564645000},"page":"425-432","source":"Crossref","is-referenced-by-count":29,"title":["<i>PTPN11<\/i>\n                    and\n                    <i>KRAS<\/i>\n                    Gene Analysis in Patients with Noonan and Noonan-Like Syndromes"],"prefix":"10.1177","volume":"14","author":[{"given":"Amanda Salem","family":"Brasil","sequence":"first","affiliation":[{"name":"Instituto da Crian\u00e7a","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre C.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Gen\u00e9tica e Cardiologia Molecular, InCor","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciana Turolla","family":"Wanderley","sequence":"additional","affiliation":[{"name":"Instituto da Crian\u00e7a","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chong Ae","family":"Kim","sequence":"additional","affiliation":[{"name":"Instituto da Crian\u00e7a","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexsandra C.","family":"Malaquias","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander A.L.","family":"Jorge","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Eduardo","family":"Krieger","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Gen\u00e9tica e Cardiologia Molecular, InCor","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D\u00e9bora Romeo","family":"Bertola","sequence":"additional","affiliation":[{"name":"Instituto da Crian\u00e7a","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2010,6,26]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1641"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20748"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/gte.2006.10.186"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-007-0146-1"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30813"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1086\/504394"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2006.04353.x"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.1086\/498454"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/341528"},{"key":"e_1_3_3_11_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2008.119545"},{"key":"e_1_3_3_12_1","unstructured":"ESE Finder. 2009. 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