{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:02:35Z","timestamp":1789567355808,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100008273","name":"\u00d8jenfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008273","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Ophthalmologica"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      To investigate the genetic and genealogical background of keratitis fugax hereditaria (KFH), a periodic corneal disease caused by the heterozygous pathogenic variant c.61G&gt;C in the\n                      <jats:italic>NLRP3<\/jats:italic>\n                      gene. KFH is characterized by recurrent unilateral autoinflammatory attacks alternating between the eyes and permanent corneal opacities.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Single\u2010nucleotide polymorphism genotyping was performed in 91 individuals from 29 families. Phased haplotypes and recombination breakpoints around the\n                      <jats:italic>NLRP3<\/jats:italic>\n                      locus were analysed. Genealogical data were collected from 32 Finnish families with KFH, including 107 genetically confirmed patients, and extended to 2756 ancestors using interviews, population registers and historical church records.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All families shared a common haplotype surrounding the disease variant, although centromeric and telomeric recombination breakpoints were variable. Differences in common haplotype lengths were consistent with varying degrees of relatedness. Genealogical data were complete for 11 families and partial for 17. Ancestral birthplaces clustered in southwestern Finland, and several families shared distant common ancestors from the mid\u2010to\u2010late 1600s, forming four principal lineages originating from a restricted geographic area.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>NLRP3<\/jats:italic>\n                      c.61G&gt;C variant likely originated in southwestern Finland and appears to have been present in the population for at least 350\u2009years. Genealogical reconstruction and haplotype analysis support a single ancestral origin, followed by lineage\u2010specific divergence and regional expansion. In the context of Finland's population history, these findings indicate long\u2010term regional enrichment of the variant and provide a historical framework for understanding its present\u2010day distribution.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aos.70238","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:04:02Z","timestamp":1789563842000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A genetic and historical perspective on the origins of keratitis fugax hereditaria"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8264-945X","authenticated-orcid":false,"given":"Annamari T.","family":"Immonen","sequence":"first","affiliation":[{"name":"Eye Genetics Group, Folkh\u00e4lsan Research Center, Biomedicum Helsinki  Helsinki Finland"},{"name":"Department of Ophthalmology University of Helsinki and Helsinki University Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4963-6862","authenticated-orcid":false,"given":"Sara P.","family":"Luostarinen","sequence":"additional","affiliation":[{"name":"Department of Philosophy, History and Arts, Faculty of Humanities University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e4ivi","family":"Lahermo","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland (FIMM) University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabita","family":"Kawan","sequence":"additional","affiliation":[{"name":"Eye Genetics Group, Folkh\u00e4lsan Research Center, Biomedicum Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kati","family":"Donner","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland (FIMM) University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph D.","family":"Terwilliger","sequence":"additional","affiliation":[{"name":"Department of Genetics and Development, Department of Psychiatry, Gertrude H. Sergievsky Center, Columbia University Irving Medical Center; Division of Medical Genetics New York State Psychiatric Institute  New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Backlund","sequence":"additional","affiliation":[{"name":"Eye Genetics Group, Folkh\u00e4lsan Research Center, Biomedicum Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9569-9146","authenticated-orcid":false,"given":"Joni A.","family":"Turunen","sequence":"additional","affiliation":[{"name":"Eye Genetics Group, Folkh\u00e4lsan Research Center, Biomedicum Helsinki  Helsinki Finland"},{"name":"Department of Ophthalmology University of Helsinki and Helsinki University Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2022.10.004"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau1043"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2025.03.004"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2021.10.025"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0000000000003399"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo-2022-321825"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng917"},{"key":"e_1_2_8_9_1","first-page":"56","article-title":"H\u00e4iden maantiede","volume":"2014","author":"Lamberg M.","year":"2014","journal-title":"Suomen Museo"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/302537"},{"key":"e_1_2_8_11_1","first-page":"284","volume-title":"Reunamailla. 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(2023)Vital statistics and population. 1749\u20132023."},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2020.02.002"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2018.01.017"},{"key":"e_1_2_8_25_1","first-page":"659","article-title":"Keratitis fugax hereditaria","volume":"80","author":"Valle O.","year":"1964","journal-title":"Duodecim"}],"container-title":["Acta Ophthalmologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aos.70238","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/aos.70238","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aos.70238","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:04:08Z","timestamp":1789563848000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/aos.70238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":24,"alternative-id":["10.1111\/aos.70238"],"URL":"https:\/\/doi.org\/10.1111\/aos.70238","archive":["Portico"],"relation":{},"ISSN":["1755-375X","1755-3768"],"issn-type":[{"value":"1755-375X","type":"print"},{"value":"1755-3768","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]},"assertion":[{"value":"2026-02-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"aos.70238"}}