{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T12:02:03Z","timestamp":1781092923348,"version":"3.54.1"},"reference-count":42,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004047","name":"Karolinska Institutet","doi-asserted-by":"publisher","award":["SLS\u20101021343"],"award-info":[{"award-number":["SLS\u20101021343"]}],"id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Ophthalmologica"],"abstract":"Abstract<\/jats:title>\n \n Purpose<\/jats:title>\n To determine the molecular cause of the two epithelial recurrent erosion dystrophies, Dystrophia Smolandiensis and Dystrophia Helsinglandica, and to identify phenotypic differences between the two conditions.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n DNA samples and clinical data from structured interview records were obtained from the Swedish families in which Dystrophia Smolandiensis and Dystrophia Helsinglandica were originally characterized. Candidate variant detection was performed using combinations of linkage analysis, Sanger sequencing, exome sequencing and genome sequencing. Differences in age of onset and precipitating factors of erosive episodes were assessed using the Wilcoxon rank sum test and Fisher's exact test.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In Dystrophia Smolandiensis, the novel candidate variant\n NQO1<\/jats:italic>\n c.535\u2009T>A p.(Phe179Ile) co\u2010segregated with disease across 49 informative meioses. In Dystrophia Helsinglandica, the known pathogenic splice variant\n COL17A1<\/jats:italic>\n c.3156C>T was identified. There were significant phenotypic differences between the two conditions. The median age of onset was lower in Dystrophia Smolandiensis (2.5\u2009years vs. 6\u2009years,\n p<\/jats:italic>\n \u2009=\u20090.00065). Cigarette smoke, intense sunlight and pregnancy were distinct precipitating factors of erosive episodes in Dystrophia Smolandiensis (\n p<\/jats:italic>\n \u2009=\u20090.0010,\n p<\/jats:italic>\n \u2009<\u20090.0001 and\n p<\/jats:italic>\n \u2009=\u20090.016, respectively), whereas minor trauma to the eye was specific to Dystrophia Helsinglandica (\n p<\/jats:italic>\n \u2009<\u20090.0001).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n NQO1<\/jats:italic>\n is a candidate gene for Dystrophia Smolandiensis, while Dystrophia Helsinglandica is synonymous with\n COL17A1<\/jats:italic>\n \u2010associated ERED. The two conditions are characterized by distinct phenotypic differences. Based on these findings, we suggest a reclassification of epithelial recurrent erosion dystrophies guided by genetics. We propose designating\n COL17A1<\/jats:italic>\n \u2010associated epithelial recurrent erosion dystrophy as ERED1 and\n NQO1<\/jats:italic>\n \u2010associated epithelial recurrent erosion dystrophy as ERED2.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/aos.70171","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T11:15:21Z","timestamp":1781090121000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dystrophia Smolandiensis is characterized by a novel\n \n NQO1<\/i>\n <\/scp>\n variant and a distinct phenotype from\n \n COL17A1<\/i>\n <\/scp>\n \u2010associated epithelial recurrent erosion dystrophy"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7849-2082","authenticated-orcid":false,"given":"Karl","family":"De Geer","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden"},{"name":"Department of Clinical Genetics and Genomics Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Lagerstedt\u2010Robinson","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden"},{"name":"Department of Clinical Genetics and Genomics Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden"},{"name":"Department of Clinical Genetics and Genomics Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cilla","family":"S\u00f6derh\u00e4ll","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health Karolinska Institutet Stockholm Sweden"},{"name":"Astrid Lindgren Children's Hospital Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0415-0535","authenticated-orcid":false,"given":"Bj\u00f6rn","family":"Hammar","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Department of Clinical Sciences Lund Lund University, Sk\u00e5ne University Hospital Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Bj\u00f6rck","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden"},{"name":"Department of Clinical Genetics and Genomics Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"Adzhubei I.A.","year":"2010","journal-title":"Nature Methods"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.abb.2005.03.015","article-title":"FAD semiquinone stability regulates single\u2010 and two\u2010electron reduction of quinones by anabaena PCC7119 ferredoxin:NADP+ reductase and its Glu301Ala mutant","volume":"437","author":"Anusevicius Z.","year":"2005","journal-title":"Archives of Biochemistry and Biophysics"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"6372","DOI":"10.1021\/bi0600087","article-title":"The crystal structure of NAD(P)H quinone oxidoreductase 1 in complex with its 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