{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:53:14Z","timestamp":1790873594412,"version":"4.1.0"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>KIT<\/jats:italic> is a proto-oncogene that is involved in the proliferation, survival, and regulation of melanocytes, mast cells, and the interstitial cells of Cajal. Mutations of <jats:italic>KIT<\/jats:italic> have been reported to be associated with hyperpigmentation and lentigines, mastocytosis, and gastrointestinal stromal tumors (GISTs). Some hotspot mutations of <jats:italic>KIT<\/jats:italic> have been reported to be associated with mastocytosis and GISTs, while the relationship between <jats:italic>KIT<\/jats:italic> mutations and hyperpigmentation and lentigines has not been fully elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we presented a three-generation Chinese pedigree with progressive hyperpigmentation and generalized lentigines inherited in an autosomal dominant pattern. High-throughput sequencing was performed to capture genetic variations in peripheral blood samples of the proband. Also, Sanger sequencing was performed to further verify the result. We also reviewed previous literature on <jats:italic>KIT<\/jats:italic> mutations with hyperpigmentation and lentigines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A missense mutation of the <jats:italic>KIT<\/jats:italic> gene was identified: c. 2485G &amp;gt; C, which was co-segregated in the proband and his insulted father. Germline <jats:italic>KIT<\/jats:italic> mutations presenting as generalized hyperpigmentation and lentigines without systemic disorders are rare, with only two reports of c. 2485G &amp;gt; C mutation associated with this phenotype in previous literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our pedigree, together with those two reports, indicates a possible phenotype-genotype correlation of this germline <jats:italic>KIT<\/jats:italic> mutation, which might be helpful for genetic counseling, further functional segregation of KIT, and design of targeted therapy in the future.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2022.847382","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T08:44:42Z","timestamp":1653468282000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Case Report: A Missense Mutation of KIT in Hyperpigmentation and Lentigines Unassociated With Systemic Disorders: Report of a Chinese Pedigree and a Literature Review"],"prefix":"10.3389","volume":"9","author":[{"given":"Lu","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehua","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1111\/pde.13952","article-title":"Novel KIT mutation presenting as marked lentiginosis","volume":"36","author":"Tran","year":"2019","journal-title":"Pediatr Dermatol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s13578-016-0120-8","article-title":"Germline mutations of KIT in gastrointestinal stromal tumor (GIST) and mastocytosis","volume":"6","author":"Ke","year":"2016","journal-title":"Cell Biosci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1007\/s40257-018-0414-1","article-title":"KIT as an Oncogenic driver in melanoma: an update on clinical development","volume":"20","author":"Meng","year":"2019","journal-title":"Am J Clin Dermatol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1159\/000077302","article-title":"c-kit Mutation in generalized lentigines associated with gastrointestinal stromal tumor","volume":"208","author":"Shibusawa","year":"2004","journal-title":"Dermatology."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.1111\/bjd.16895","article-title":"Autosomal dominant progressive hyperpigmentation and lentigines in a Japanese pedigree due to a missense mutation near the C-terminus of KIT","volume":"179","author":"Takeichi","year":"2018","journal-title":"Br J Dermatol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1111\/ced.13757","article-title":"Cutaneous hyperpigmentation and familial gastrointestinal stromal tumour associated with KIT mutation","volume":"44","author":"Wali","year":"2019","journal-title":"Clin Exp Dermatol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e241","DOI":"10.1111\/1346-8138.15321","article-title":"Generalized lentigines associated with familial gastrointestinal stromal tumors dramatically improved by imatinib treatment","volume":"47","author":"Hasegawa","year":"2020","journal-title":"J Dermatol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e148","DOI":"10.1111\/bjd.19295","article-title":"Multiple lentigines and cutaneous hyperpigmentation caused by a KIT mutation","volume":"183","author":"Jiang","year":"2020","journal-title":"Br J Dermatol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1111\/pcmr.12107","article-title":"Secondary c-Kit mutations confer acquired resistance to RTK inhibitors in c-Kit mutant melanoma cells","volume":"26","author":"Todd","year":"2013","journal-title":"Pigment Cell Melanoma Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1097\/CCO.0000000000000606","article-title":"Targeted therapies in melanoma beyond BRAF: targeting NRAS-mutated and KIT-mutated melanoma","volume":"32","author":"Delyon","year":"2020","journal-title":"Curr Opin Oncol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"31","DOI":"10.21037\/atm-21-4235","article-title":"BRAF, C-KIT, and NRAS 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