{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T07:40:15Z","timestamp":1792309215344,"version":"4.4.0"},"reference-count":28,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Research Council of Finland","doi-asserted-by":"publisher","award":["368449"],"award-info":[{"award-number":["368449"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Thoracic aortic aneurysms and dissections are major causes of sudden cardiovascular death. We aimed to evaluate the clinical significance of the\n                      <jats:italic>MYLK<\/jats:italic>\n                      c.4079G&gt;A, p.(Gly1360Asp) variant in Finnish families with heritable thoracic aortic disease (HTAD) and to assess evidence for a potential founder effect.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We evaluated the clinical significance and potential founder effect of the missense variant\n                      <jats:italic>MYLK<\/jats:italic>\n                      c.4079G&gt;A, p.(Gly1360Asp) in Finnish families. Eight individuals from four unrelated Finnish families carrying the\n                      <jats:italic>MYLK<\/jats:italic>\n                      c.4079G&gt;A heterozygous variant were recruited. Clinical histories, imaging data, and pedigrees were reviewed. Genetic testing included exome\u2011based gene panel sequencing or targeted familial variant testing. Variant classification followed the American College of Medical Genetics and Genomics 2015 guidelines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thoracic aortic dilatation or aneurysm occurred in 6\/8 carriers (75%), with a mean age at diagnosis of 45 years (range 34\u201367). Ascending aortic diameters ranged from 26\u201359\u00a0mm, most often measured at the aortic root. Aortic dissection occurred in 4\/8 (50%) at a mean age of 46 years (range 34\u201368), including three early\u2011adult events. Extrathoracic arterial involvement (carotid) was observed in one variant\u2011positive individual.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>MYLK<\/jats:italic>\n                      c.4079G&gt;A, p.(Gly1360Asp) variant was present in six affected individuals from four unrelated families and is enriched in the Finnish population, supporting a founder effect. The\n                      <jats:italic>MYLK<\/jats:italic>\n                      c.4079G&gt;A, p.(Gly1360Asp) variant is associated with early\u2011adult\u2011onset, high\u2011penetrance thoracic aortic disease and substantial dissection risk, underscoring the need for vigilant surveillance and early intervention in affected individuals and at\u2011risk relatives.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ahg.70064","type":"journal-article","created":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T07:04:37Z","timestamp":1792307077000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>MYLK<\/i>\n                    c.4079G&gt;A, p.(Gly1360Asp) Variant Associated With Hereditary Thoracic Aortic Diseases and Early Onset Aortic Dissection"],"prefix":"10.1111","author":[{"given":"Minja","family":"Virtanen","sequence":"first","affiliation":[{"name":"Department of Genomics Turku University Hospital  Turku Finland"},{"name":"Faculty of Science University of Turku  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sini","family":"Keskinen","sequence":"additional","affiliation":[{"name":"Department of Genomics Turku University Hospital  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikhard","family":"Bj\u00f6rn","sequence":"additional","affiliation":[{"name":"Heart Center Turku University Hospital University of Turku  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minna","family":"Paavola","sequence":"additional","affiliation":[{"name":"Department of Genomics Turku University Hospital  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Pohjola","sequence":"additional","affiliation":[{"name":"Department of Genomics Turku University Hospital  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marja","family":"Hietala","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Turku University Hospital  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria K.","family":"Haanp\u00e4\u00e4","sequence":"additional","affiliation":[{"name":"Department of Genomics Turku University Hospital  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Malmberg","sequence":"additional","affiliation":[{"name":"Heart Center Turku University Hospital University of Turku  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Rahikkala","sequence":"additional","affiliation":[{"name":"Department of Genomics Turku University Hospital  Turku Finland"},{"name":"Research Unit of Clinical Medicine and Medical Research Center Oulu University of Oulu and University Hospital  Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4797"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","unstructured":"Backer J. F. A. L. M.Mosquera J. F.Rodriguez\u2010Palomares andG.Teixido\u2010Tura.2026.\u201cDiagnosis and Management of Heritable Thoracic Aortic Diseases.\u201d Heart ahead of print February 4.https:\/\/doi.org\/10.1136\/heartjnl\u20102025\u2010326230.","DOI":"10.1136\/heartjnl-2025-326230"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1082"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.63458"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2025.1672342"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2022.104673"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006045\u20100"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2026.02.034"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.21.10114"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/152165401753366087"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2022.2718"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2000.279.5.C1656"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201511483"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvir.2021.100747"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.009762"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2022.08.004"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/HCO.0000000000000114"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1134\/S000629791613006X"},{"key":"e_1_2_11_20_1","doi-asserted-by":"crossref","first-page":"D980","DOI":"10.1093\/nar\/gkt1113","article-title":"ClinVar: Public Archive of Relationships Among Sequence Variation and Human Phenotype","volume":"42","author":"Landrum M. J.","year":"2014","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi901963e"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/4281972"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcts.2008.12.047"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.312436"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2023.108009"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010018\u20100038\u20100"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.10.006"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2018.07.047"}],"container-title":["Annals of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ahg.70064","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ahg.70064","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ahg.70064","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T07:04:38Z","timestamp":1792307078000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ahg.70064"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,18]]},"references-count":28,"alternative-id":["10.1111\/ahg.70064"],"URL":"https:\/\/doi.org\/10.1111\/ahg.70064","archive":["Portico"],"relation":{},"ISSN":["0003-4800","1469-1809"],"issn-type":[{"value":"0003-4800","type":"print"},{"value":"1469-1809","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,18]]},"assertion":[{"value":"2026-05-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ahg.70064"}}