{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:02:36Z","timestamp":1789642956065,"version":"4.0.0"},"reference-count":18,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,8,13]],"date-time":"2014-08-13T00:00:00Z","timestamp":1407888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"crossref","award":["2011\/17299-3"],"award-info":[{"award-number":["2011\/17299-3"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:sec><jats:label\/><jats:p>Noonan syndrome (NS) is an autosomal dominant disorder consisting of short stature, short and\/or webbed neck, distinctive facial features, cardiac abnormalities, cryptorchidism, and coagulation defects. NS exhibits genetic heterogeneity, associated with mutated genes that participate in RAS\u2010mitogen\u2010activated protein kinase signal transduction. Recently, a new gene (<jats:italic>RIT1<\/jats:italic>) was discovered as the causative gene in 17 of 180 Japanese individuals who were negative for the previously known genes for NS and were studied using exome sequencing (four patients), followed by Sanger sequencing (13 patients). The present study used the same technique in 70 Brazilian patients with NS and identified six with <jats:italic>RIT1<\/jats:italic> missense mutations. Thus, we confirm that <jats:italic>RIT1<\/jats:italic> is responsible for approximately 10% of the patients negative for mutations in the previously known genes. The phenotype includes a high frequency of high birth weight, relative macrocephaly, left ventricular hypertrophy, and ectodermal findings, such as curly hair, hyperpigmentation, and wrinkled palms and soles. Short stature and pectus deformity were less frequent. The majority of patients with a <jats:italic>RIT1<\/jats:italic> mutation did not show apparent intellectual disability. Because of the relatively high frequency of mutations in <jats:italic>RIT1<\/jats:italic> among patients with NS and its occurrence in different populations, we suggest that it should be added to the list of genes included in panels for the molecular diagnosis of NS through targeted next\u2010generation sequencing. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36722","type":"journal-article","created":{"date-parts":[[2014,8,13]],"date-time":"2014-08-13T22:01:19Z","timestamp":1407967279000},"page":"2952-2957","source":"Crossref","is-referenced-by-count":56,"title":["Further evidence of the importance of <i>RIT1<\/i> in Noonan syndrome"],"prefix":"10.1002","volume":"164","author":[{"given":"D\u00e9bora R.","family":"Bertola","sequence":"first","affiliation":[{"name":"Unidade de Gen\u00e9tica do Instituto da Crian\u00e7a Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo S\u00e3o Paulo\/SP Brazil"},{"name":"Instituto de Bioci\u00eancias Universidade de S\u00e3o Paulo S\u00e3o Paulo\/SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme L.","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica do Instituto da Crian\u00e7a Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo S\u00e3o Paulo\/SP Brazil"},{"name":"Instituto de Bioci\u00eancias Universidade de S\u00e3o Paulo S\u00e3o Paulo\/SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana F.","family":"Almeida","sequence":"additional","affiliation":[{"name":"Instituto de Bioci\u00eancias Universidade de S\u00e3o Paulo S\u00e3o Paulo\/SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Buscarilli","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica do Instituto da Crian\u00e7a Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo S\u00e3o Paulo\/SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander A. L.","family":"Jorge","sequence":"additional","affiliation":[{"name":"Endocrinologia LIM\/25 Faculdade de Medicina da Universidade de S\u00e3o Paulo S\u00e3o Paulo\/SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexsandra C.","family":"Malaquias","sequence":"additional","affiliation":[{"name":"Endocrinologia LIM\/25 Faculdade de Medicina da Universidade de S\u00e3o Paulo S\u00e3o Paulo\/SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong A.","family":"Kim","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica do Instituto da Crian\u00e7a Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo S\u00e3o Paulo\/SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa N. 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