{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:07:08Z","timestamp":1792084028617,"version":"4.4.0"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,4,29]],"date-time":"2016-04-29T00:00:00Z","timestamp":1461888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["ZE 524\/10\u20101"],"award-info":[{"award-number":["ZE 524\/10\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["HE 6743\/2\u20101"],"award-info":[{"award-number":["HE 6743\/2\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["HE 6743\/3\u20101"],"award-info":[{"award-number":["HE 6743\/3\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["RE 3777\/1\u20101"],"award-info":[{"award-number":["RE 3777\/1\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CU47\/6\u20101"],"award-info":[{"award-number":["CU47\/6\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CU47\/12\u20101"],"award-info":[{"award-number":["CU47\/12\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2016,10]]},"abstract":"Oculoectodermal syndrome (OES<\/jats:styled-content>) and encephalocraniocutaneous lipomatosis (ECCL<\/jats:styled-content>) are rare disorders that share many common features, such as epibulbar dermoids, aplasia cutis congenita, pigmentary changes following Blaschko lines, bony tumor\u2010like lesions, and others. About 20 cases with OES<\/jats:styled-content> and more than 50 patients with ECCL<\/jats:styled-content> have been reported. Both diseases were proposed to represent mosaic disorders, but only very recently whole\u2010genome sequencing has led to the identification of somatic KRAS<\/jats:styled-content><\/jats:italic> mutations, p.Leu19Phe<\/jats:styled-content> and p.Gly13Asp<\/jats:styled-content>, in affected tissue from two individuals with OES<\/jats:styled-content>. Here we report the results of molecular genetic studies in three patients with OES<\/jats:styled-content> and one with ECCL<\/jats:styled-content>. In all four cases, Sanger sequencing of the KRAS<\/jats:styled-content><\/jats:italic> gene in DNA<\/jats:styled-content> from lesional tissue detected mutations affecting codon 146 (p.Ala146Val<\/jats:styled-content>, p.Ala146Thr<\/jats:styled-content>) at variable levels of mosaicism. Our findings thus corroborate the evidence of OES<\/jats:styled-content> being a mosaic RASopathy<\/jats:styled-content> and confirm the common etiology of OES<\/jats:styled-content> and ECCL<\/jats:styled-content>. KRAS<\/jats:styled-content><\/jats:italic> codon 146 mutations, as well as the previously reported OES<\/jats:styled-content>\u2010associated alterations, are known oncogenic KRAS<\/jats:styled-content><\/jats:italic> mutations with distinct functional consequences. Considering the phenotype and genotype spectrum of mosaic RASopathies<\/jats:styled-content>, these findings suggest that the wide phenotypic variability does not only depend on the tissue distribution but also on the specific genotype.<\/jats:p>","DOI":"10.1111\/cge.12775","type":"journal-article","created":{"date-parts":[[2016,3,12]],"date-time":"2016-03-12T20:14:06Z","timestamp":1457813646000},"page":"334-342","source":"Crossref","is-referenced-by-count":71,"title":["Specific mosaic KRAS<\/scp><\/i> mutations affecting codon 146 cause oculoectodermal syndrome and encephalocraniocutaneous lipomatosis"],"prefix":"10.1111","volume":"90","author":[{"given":"S.","family":"Boppudi","sequence":"first","affiliation":[{"name":"Institute of Human Genetics University Hospital Magdeburg, Otto\u2010von\u2010Guericke University Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"B\u00f6gershausen","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Medical Center Goettingen, Georg\u2010August University Goettingen Germany"},{"name":"Institute of Human Genetics University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.B.","family":"Hove","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Copenhagen University Hospital Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.F.","family":"Percin","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine Gazi University Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Aslan","sequence":"additional","affiliation":[{"name":"Section of Hematology, Department of Pediatrics, Faculty of Medicine Gazi University Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Dvorsky","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology II, Medical Faculty Heinrich\u2010Heine\u2010University D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Kayhan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine Gazi University Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Medical Center Goettingen, Georg\u2010August University Goettingen Germany"},{"name":"Institute of Human Genetics University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Cursiefen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Tantcheva\u2010Poor","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.B.","family":"Toft","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Copenhagen University Hospital Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Bartsch","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Medical Centre of the Johannes Gutenberg University Mainz Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Lissewski","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Hospital Magdeburg, Otto\u2010von\u2010Guericke University Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Wieland","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Hospital Magdeburg, Otto\u2010von\u2010Guericke University Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Jakubiczka","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Hospital Magdeburg, Otto\u2010von\u2010Guericke University Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Wollnik","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Medical Center Goettingen, Georg\u2010August University Goettingen Germany"},{"name":"Institute of Human Genetics University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.R.","family":"Ahmadian","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology II, Medical Faculty Heinrich\u2010Heine\u2010University D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.M.","family":"Heindl","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Zenker","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Hospital Magdeburg, Otto\u2010von\u2010Guericke University Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,4,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320450620"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31969"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37048"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.84.6.667c"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00019605-200404000-00005"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.066068"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000017968"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32074"},{"key":"e_1_2_9_10_1","article-title":"Oculoectodermal syndrome: a new case with giant cell granulomas and non\u2010ossifying fibromas","author":"Mermer S","year":"2015","journal-title":"Genet Counsel"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36727"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2009.04.001"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0b013e32834881dd"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2006.12.004"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21377"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32227"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20431"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31456"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32639"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37439"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2014.244"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30300"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(20000424)91:5<391::AID-AJMG14>3.0.CO;2-F"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.188"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.447"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2015.03.013"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-15-0203"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1062023"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.8.6.2472"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.11.091"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605534"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-2612"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.5.8.3251"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2014.195"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.14105"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2316"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.379"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.377"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajd.12399"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3343\/alm.2015.35.1.178"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37135"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-015-0247-1"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100637"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37376"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.24"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2014.6"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.429"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.70"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.2350\/14-10-1566-OA.1"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.430"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt429"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.12775","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.12775","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T21:32:17Z","timestamp":1696368737000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.12775"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,29]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["10.1111\/cge.12775"],"URL":"https:\/\/doi.org\/10.1111\/cge.12775","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,29]]}}}