{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:56:22Z","timestamp":1791446182016,"version":"4.3.3"},"reference-count":15,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Postzygotic somatic variants affecting the Ras\/MAPK signaling pathway can cause mosaic RASopathies, characterized by craniofacial abnormalities, cardiac defects, growth impairment, and various cutaneous manifestations in localized areas of the body. Herein, we present a rare case of mosaic RASopathy caused by a somatic\n HRAS<\/jats:italic>\n variant. A 52\u2010year\u2010old Japanese patient visited our department because of skin metastasis of malignant melanoma. Besides, he had a sebaceous nevus on the forehead, linear epidermal nevus on the trunk along with the Blaschko line, and focal and linear non\u2010epidermolytic palmoplantar keratoderma since he was young. Genetic testing revealed an\n HRAS<\/jats:italic>\n missense variant c.34G>A (p.Gly12Ser) in the cells of sebaceous nevus, pigmented skin lesion, palmoplantar keratoderma, and metastatic skin lesion of melanoma. In contrast, no pathogenic\n HRAS<\/jats:italic>\n variant was detected in peripheral blood leukocytes or in clinically normal skin. Somatic mutations in\n HRAS<\/jats:italic>\n can cause mosaic Costello syndrome, Schimmelpenning syndrome, and woolly hair nevus. However, there is some overlap in clinical manifestations among these diseases, and no clear diagnostic criteria have been established. Therefore, we diagnosed this case as\n HRA<\/jats:italic>\n S\u2010mutant mosaic RASopathy. In addition, this is the first reported case of mosaic RASopathy concomitant with malignant melanoma. Although the occurrence of concurrent melanoma would be coincidental in this case, further investigation is necessary to evaluate the precise association between\n HRAS<\/jats:italic>\n \u2010mutant mosaic RASopathy and melanoma. The melanoma cells showed a high proportion of mutant alleles, possibly due to loss of heterozygosity. Further investigation is necessary to evaluate the precise association between\n HRAS<\/jats:italic>\n \u2010mutant mosaic RASopathy and melanoma.\n <\/jats:p>","DOI":"10.1111\/1346-8138.70421","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T04:03:07Z","timestamp":1784865787000},"page":"1547-1551","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mosaic\n RASopathy<\/scp>\n Caused by a Somatic\n \n HRAS<\/i>\n <\/scp>\n p.\n Gly12Ser<\/scp>\n Variant in a Patient With Malignant Melanoma"],"prefix":"10.1111","volume":"53","author":[{"given":"Chihiro","family":"Sagara","sequence":"first","affiliation":[{"name":"Department of Dermatology Hirosaki University Graduate School of Medicine Hirosaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yihan","sequence":"additional","affiliation":[{"name":"Department of Dermatology Hirosaki University 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