{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T20:13:35Z","timestamp":1778616815945,"version":"3.51.4"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T00:00:00Z","timestamp":1580083200000},"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":["Pigment Cell Melanoma Res"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Dyschromatosis symmetrica hereditaria (DSH) is a pigmentary genodermatosis caused by mutations in <jats:italic>ADAR1<\/jats:italic>. In this study, we performed mutation analysis on a family that included typical DSH patients. No mutations were found in any coding regions or exon\u2013intron boundary regions of <jats:italic>ADAR1<\/jats:italic>, but a previously unreported non\u2010coding heterozygous variant, c.\u201060A&gt;G, was found in the 5\u2032 untranslated region (5\u2032UTR) of <jats:italic>ADAR1<\/jats:italic> in the proband and her mother. The function of 5\u2032UTR in mRNA is not well\u2010understood. To understand the pathogenesis of the variant and the function of the 5\u2032UTR of <jats:italic>ADAR1<\/jats:italic>, we constructed two reporter genes carrying the <jats:italic>ADAR1<\/jats:italic> 5\u2032UTR sequence with\/without the variant between the PGK promoter and a luciferase coding sequence, and performed luciferase assays, semi\u2010quantitative PCR analyses, and polysomal assays. In human melanocytes, c.\u201060A&gt;G induced a 16% reduction in transcription and a 51% reduction in translation. Our results indicate that the 5\u2032UTR c.\u201060A&gt;G variant adversely affects the post\u2010transcriptional step in gene expression, leading to DSH. Detailed functional assays of the 5\u2032UTR of <jats:italic>ADAR1<\/jats:italic> in the present study revealed the gene expression to be not only downregulated, but also upregulated by defects in 5\u2032UTR depending on the locations. The regulation of translation by 5\u2032UTR is very complicated.<\/jats:p>","DOI":"10.1111\/pcmr.12863","type":"journal-article","created":{"date-parts":[[2020,1,11]],"date-time":"2020-01-11T14:41:33Z","timestamp":1578753693000},"page":"591-600","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pathogenesis of a variant in the 5\u2032 untranslated region of ADAR1 in dyschromatosis symmetrica hereditaria"],"prefix":"10.1111","volume":"33","author":[{"given":"Mutsumi","family":"Suganuma","sequence":"first","affiliation":[{"name":"Department of Dermatology Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2639-1583","authenticated-orcid":false,"given":"Michihiro","family":"Kono","sequence":"additional","affiliation":[{"name":"Department of Dermatology Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayoshi","family":"Yamanaka","sequence":"additional","affiliation":[{"name":"Division of Dermatology Ishii Hospital Isezaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Akiyama","sequence":"additional","affiliation":[{"name":"Department of Dermatology Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,1,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003529"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq022"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0810916106"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22899"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2004.11.007"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2014.0001"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1680"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1346-8138.2012.01661.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0331231"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.09.057"},{"issue":"2","key":"e_1_2_8_12_1","first-page":"267","article-title":"Analysis of genotype\/phenotype correlations in Japanese patients with dyschromatosis symmetrica hereditaria","volume":"80","author":"Kobayashi T.","year":"2018","journal-title":"Nagoya Journal of Medical Science"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2019.01.004"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2015.12.034"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.16610"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.15076"},{"issue":"30","key":"e_1_2_8_17_1","doi-asserted-by":"crossref","first-page":"19867","DOI":"10.1016\/S0021-9258(18)54860-2","article-title":"Structural features in eukaryotic mRNAs that modulate the initiation of translation","volume":"266","author":"Kozak M.","year":"1991","journal-title":"Journal of Biological Chemistry"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-002-4002-5"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1153"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2003-4-7-223"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60327-429-6_1"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1086\/378209"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.10.5376"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.125"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-019-0564-x"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2010.12.004"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2142"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10212"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-202X.2005.23732.x"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700528"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt015"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310162200"}],"container-title":["Pigment Cell &amp; 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