{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T11:45:08Z","timestamp":1774266308858,"version":"3.50.1"},"reference-count":13,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T00:00:00Z","timestamp":1559865600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP18ek0109301"],"award-info":[{"award-number":["JP18ek0109301"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Activation of the RAS pathway through either the activation of genes that accelerate the pathway or the suppression of genes that inhibit the pathway leads to a group of disorders collectively referred to as RASopathies. The key molecules of the RAS pathway are <jats:italic>KRAS<\/jats:italic>, <jats:italic>HRAS<\/jats:italic>, and <jats:italic>NRAS<\/jats:italic>. Mutations in these three RAS homolog genes have been shown to be associated with RASopathies. Recently, two patients with a Noonan syndrome phenotype were shown to carry mutations in the yet another RASopathy gene, <jats:italic>MRAS<\/jats:italic> (muscle RAS oncogene homolog). Here, we report a patient with a severe Noonan syndrome phenotype associated with a germline Q71R MRAS variant, which represents a recurrent substitution in RAS homologs in various cancers. The patient's dysmorphic features included relative macrocephaly, a down\u2010slanted palpebral fissure, hypertelorism, a depressed nasal bridge, and low\u2010set ears with thick lobes; these facial features are strongly associated with RASopathy. We confirmed that the <jats:italic>MRAS<\/jats:italic> gene represents a causative gene for RASopathy.<\/jats:p>","DOI":"10.1002\/ajmg.a.61261","type":"journal-article","created":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T09:14:11Z","timestamp":1559898851000},"page":"1628-1630","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Severe Noonan syndrome phenotype associated with a germline Q71R MRAS variant: a recurrent substitution in RAS homologs in various cancers"],"prefix":"10.1002","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8122-7180","authenticated-orcid":false,"given":"Hisato","family":"Suzuki","sequence":"first","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7311-4135","authenticated-orcid":false,"given":"Toshiki","family":"Takenouchi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Keio University School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1497-7686","authenticated-orcid":false,"given":"Tomoko","family":"Uehara","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Takasago","sequence":"additional","affiliation":[{"name":"Department of Cardiology Tokyo Metropolitan Children's Medical Center  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Ihara","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Tokyo Metropolitan Children's Medical Center  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Yoshihashi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Tokyo Metropolitan Children's Medical Center  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenjiro","family":"Kosaki","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,6,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37736"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.05.021"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1641"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-14-0729"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(86)90495-2"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21377"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.0b013e31822dd91f"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0279-0"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.91225"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1124642"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2009-3207"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2014.10.015"}],"container-title":["American 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