{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:04:35Z","timestamp":1789643075877,"version":"4.0.0"},"reference-count":30,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2017,9,8]],"date-time":"2017-09-08T00:00:00Z","timestamp":1504828800000},"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":[[2017,11]]},"abstract":"<jats:sec><jats:label\/><jats:p>Noonan syndrome (NS) is an autosomal dominant multisystem condition with a variable phenotype. The most characteristic features are short stature, congenital heart defects, and recognizable facial features. Mutations in SOS1 are found in 10\u201320% of patients with NS. Different genotype\u2013phenotype studies mention correlations between SOS1 mutations and some features, such as ectodermal abnormalities and specific facial features. We present a large NS family with a novel pathogenic mutation; SOS1 c.3134C&gt;G, p.Pro1045Arg. Ten family members with NS are included with genetically confirmed mutation and clinical evaluation. The phenotype shows a broad spectrum from only few suggestive features for NS in the older generation to typical features in the youngest generation. We report on a novel pathogenic mutation in the SOS1 gene and a large clinical spectrum in a NS family with ten genetically confirmed affected individuals.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38466","type":"journal-article","created":{"date-parts":[[2017,9,8]],"date-time":"2017-09-08T10:55:36Z","timestamp":1504868136000},"page":"2968-2972","source":"Crossref","is-referenced-by-count":8,"title":["Variable phenotypic expression in a large Noonan syndrome family segregating a novel SOS1 mutation"],"prefix":"10.1002","volume":"173","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1635-7410","authenticated-orcid":false,"given":"Doroth\u00e9e C.","family":"van Trier","sequence":"first","affiliation":[{"name":"Department of Pediatrics Radboud University Medical Center Amalia Children's Hospital Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuula","family":"Rinne","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kees","family":"Noordam","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Radboud University Medical Center Amalia Children's Hospital Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos M.","family":"Draaisma","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Radboud University Medical Center Amalia Children's Hospital Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ineke","family":"van der Burgt","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320210313"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33518"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.05.021"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2015.114"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0004-27302010000800009"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1315798111"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.497"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.425"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22834"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33987"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37781"},{"key":"e_1_2_7_13_1","first-page":"e91225","article-title":"Elucidation of MRAS\u2010mediated Noonan syndrome with cardiac hypertrophy","volume":"2","author":"Higgins E. 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