{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:07:06Z","timestamp":1792084026765,"version":"4.4.0"},"reference-count":47,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,5,30]],"date-time":"2021-05-30T00:00:00Z","timestamp":1622332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Mosaic\n                    <jats:italic>KRAS<\/jats:italic>\n                    variants and other RASopathy genes cause oculoectodermal, encephalo\u2010cranio\u2010cutaneous lipomatosis, and Schimmelpenning\u2010Feuerstein\u2010Mims syndromes, and a spectrum of vascular malformations, overgrowth and other associated anomalies, the latter of which are only recently being characterized. We describe eight individuals in total (six unreported cases and two previously reported cases) with somatic\n                    <jats:italic>KRAS<\/jats:italic>\n                    variants and variably associated features. Given the findings of somatic overgrowth (in seven individuals) and vascular or lymphatic malformations (in eight individuals), we suggest mosaic RASopathies (mosaic\n                    <jats:italic>KRAS<\/jats:italic>\n                    variants) be considered in the differential diagnosis for individuals presenting with asymmetric overgrowth and lymphatic or vascular anomalies. We expand the association with embryonal tumors, including the third report of embryonal rhabdomyosarcoma, as well as novel findings of Wilms tumor and nephroblastomatosis in two individuals. Rare or novel findings in our series include the presence of epilepsy, polycystic kidneys, and T\u2010cell deficiency in one individual, and multifocal lytic bone lesions in two individuals. Finally, we describe the first use of targeted therapy with a MEK inhibitor for an individual with a mosaic\n                    <jats:italic>KRAS<\/jats:italic>\n                    variant. The purposes of this report are to expand the phenotypic spectrum of mosaic\n                    <jats:italic>KRAS<\/jats:italic>\n                    \u2010related disorders, and to propose possible mechanisms of pathogenesis, and surveillance of its associated findings.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.62356","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T02:56:27Z","timestamp":1622429787000},"page":"2829-2845","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Novel findings and expansion of phenotype in a mosaic\n                    <scp>RASopathy<\/scp>\n                    caused by somatic\n                    <scp>\n                      <i>KRAS<\/i>\n                    <\/scp>\n                    variants"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4088-6673","authenticated-orcid":false,"given":"Caitlin A.","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Medical Genetics BC Women and Children's Hospital  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee","family":"Perrier","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Alberta Children's Hospital  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle C.","family":"Kurek","sequence":"additional","affiliation":[{"name":"Department of Pathology Alberta Children's Hospital  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juvianee","family":"Estrada\u2010Veras","sequence":"additional","affiliation":[{"name":"Medical Genetics Service, Walter Reed National Military Medical Center, Henry M. Jackson Foundation for the Advancement of Military Medicine Uniformed Services University of the Health Sciences  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Lehman","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics BC Women and Children's Hospital  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Yip","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Laboratory Medicine University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenda","family":"Hendson","sequence":"additional","affiliation":[{"name":"Department of Pathology BC Women and Children's Hospital  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Diamond","sequence":"additional","affiliation":[{"name":"Department of Hematology\u2014Oncology University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason W.","family":"Pinchot","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Arkin","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth A.","family":"Drolet","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie P.","family":"Napier","sequence":"additional","affiliation":[{"name":"Medical Genetics Program of Southwestern Ontario London Health Sciences Centre  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A.","family":"O'Neill","sequence":"additional","affiliation":[{"name":"Medical Genetics Program of Southwestern Ontario London Health Sciences Centre  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5409-8387","authenticated-orcid":false,"given":"Tugce B.","family":"Balci","sequence":"additional","affiliation":[{"name":"Medical Genetics Program of Southwestern Ontario London Health Sciences Centre  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim M.","family":"Keppler\u2010Noreuil","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism, Department of Pediatrics University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI98589"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5216"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12775"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.075374"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.625"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.08.006"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33954"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-015-0146-5"},{"issue":"1","key":"e_1_2_10_10_1","first-page":"652","article-title":"COSMIC (the catalogue of somatic mutations in cancer): A resource to investigate acquired mutations in human cancer","volume":"38","author":"Forbes S. 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