{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:29:31Z","timestamp":1790555371607,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,4,2]],"date-time":"2013-04-02T00:00:00Z","timestamp":1364860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:p><jats:styled-content style=\"fixed-case\">RASopathies<\/jats:styled-content> are a class of genetic syndromes caused by germline mutations in genes encoding Ras\/mitogen\u2010activated protein kinase (Ras\/<jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content>) pathway components. Cardio\u2010facio\u2010cutaneous (<jats:styled-content style=\"fixed-case\">CFC<\/jats:styled-content>) syndrome is a <jats:styled-content style=\"fixed-case\">RASopathy<\/jats:styled-content> characterized by distinctive craniofacial features, skin and hair abnormalities, and congenital heart defects caused by activating mutations of <jats:italic><jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">MEK1<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">MEK2<\/jats:styled-content><\/jats:italic>, and <jats:italic><jats:styled-content style=\"fixed-case\">KRAS<\/jats:styled-content><\/jats:italic>. We define the phenotype of seven patients with <jats:italic>de novo<\/jats:italic> deletions of chromosome 19p13.3 including <jats:italic><jats:styled-content style=\"fixed-case\">MEK2<\/jats:styled-content><\/jats:italic>; they present with a distinct phenotype but have overlapping features with <jats:styled-content style=\"fixed-case\">CFC<\/jats:styled-content> syndrome. Phenotypic features of all seven patients include tall forehead, thick nasal tip, underdeveloped cheekbones, long midface, sinuous upper vermilion border, tall chin, angular jaw, and facial asymmetry. Patients also have developmental delay, hypotonia, heart abnormalities, failure to thrive, obstructive sleep apnea, gastroesophageal reflux and integument abnormalities. Analysis of epidermal growth factor\u2010stimulated fibroblasts revealed that P\u2010<jats:styled-content style=\"fixed-case\">MEK1<\/jats:styled-content>\/2 was \u223c50% less abundant in cells carrying the <jats:italic><jats:styled-content style=\"fixed-case\">MEK2<\/jats:styled-content><\/jats:italic> deletion compared to the control. Significant differences in total <jats:styled-content style=\"fixed-case\">MEK2<\/jats:styled-content> and Sprouty1 abundance were also observed. Our cohort of seven individuals with <jats:italic><jats:styled-content style=\"fixed-case\">MEK2<\/jats:styled-content><\/jats:italic> deletions has overlapping features associated with <jats:styled-content style=\"fixed-case\">RASopathies<\/jats:styled-content>. This is the first report suggesting that, in addition to activating mutations, <jats:italic><jats:styled-content style=\"fixed-case\">MEK2<\/jats:styled-content><\/jats:italic> haploinsufficiency can lead to dysregulation of the <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> pathway.<\/jats:p>","DOI":"10.1111\/cge.12116","type":"journal-article","created":{"date-parts":[[2013,2,4]],"date-time":"2013-02-04T19:22:15Z","timestamp":1360005735000},"page":"138-146","source":"Crossref","is-referenced-by-count":33,"title":["Deletion of <i>MAP2K2\/MEK2<\/i>: a novel mechanism for a RASopathy?"],"prefix":"10.1111","volume":"85","author":[{"given":"M.J.M.","family":"Nowaczyk","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Medicine McMaster University  Hamilton Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.A.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Zeesman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U.","family":"Moog","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Heidelberg University  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.A.","family":"Sanchez\u2010Lara","sequence":"additional","affiliation":[{"name":"Children's Hospital Los Angeles, Departments of Pathology and Pediatrics, Keck School of Medicine; 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