{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:32:38Z","timestamp":1783571558071,"version":"3.55.0"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T00:00:00Z","timestamp":1673827200000},"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":["Annals of Neurology"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Heritability of stroke is assumed not to be low, especially in the young stroke population. However, most genetic studies have been performed in highly selected patients with typical clinical or neuroimaging characteristics. We investigated the prevalence of 15 Mendelian stroke genes and explored the relationships between variants and the clinical and neuroimaging characteristics in a large, unselected, young stroke population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We enrolled patients aged \u226455\u2009years with stroke or transient ischemic attack from a prospective, nationwide, multicenter stroke registry. We identified clinically relevant genetic variants (CRGVs) in 15 Mendelian stroke genes (<jats:italic>GLA<\/jats:italic>, <jats:italic>NOTCH3<\/jats:italic>, <jats:italic>HTRA1<\/jats:italic>, <jats:italic>RNF213<\/jats:italic>, <jats:italic>ACVRL1<\/jats:italic>, <jats:italic>ENG<\/jats:italic>, <jats:italic>CBS<\/jats:italic>, <jats:italic>TREX1<\/jats:italic>, <jats:italic>ABCC6<\/jats:italic>, <jats:italic>COL4A1<\/jats:italic>, <jats:italic>FBN1<\/jats:italic>, <jats:italic>NF1<\/jats:italic>, <jats:italic>COL3A1<\/jats:italic>, <jats:italic>MT\u2010TL1<\/jats:italic>, and <jats:italic>APP<\/jats:italic>) using a customized, targeted next generation sequencing panel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 1,033 patients, 131 (12.7%) had 28 CRGVs, most frequently in <jats:italic>RNF213<\/jats:italic> (n\u00a0=\u00a059), followed by <jats:italic>ABCC6<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u200953) and <jats:italic>NOTCH3<\/jats:italic> (n\u00a0=\u00a015). The frequency of CRGVs differed by ischemic stroke subtypes (<jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.01): the highest in other determined etiology (20.1%), followed by large artery atherosclerosis (13.6%). It also differed between patients aged \u226435\u2009years and those aged 51 to 55\u2009years (17.1% vs 9.3%, <jats:italic>p<\/jats:italic>\u00a0=\u20090.02). Only 27.1% and 26.7% of patients with <jats:italic>RNF213<\/jats:italic> and <jats:italic>NOTCH3<\/jats:italic> variants had typical neuroimaging features of the corresponding disorders, respectively. Variants of uncertain significance (VUSs) were found in 15.4% patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>CRGVs in 15 Mendelian stroke genes may not be uncommon in the young stroke population. The majority of patients with CRGVs did not have typical features of the corresponding monogenic disorders. Clinical implications of having CRGVs or VUSs should be explored. ANN NEUROL 2023;93:768\u2013782<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.26575","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T12:50:27Z","timestamp":1671627027000},"page":"768-782","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Prevalence of Mutations in Mendelian Stroke Genes in Early Onset Stroke Patients"],"prefix":"10.1002","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8120-2469","authenticated-orcid":false,"given":"Hong\u2010Kyun","family":"Park","sequence":"first","affiliation":[{"name":"Department of Neurology Inje University Ilsan Paik Hospital, Inje University College of Medicine  Goyang South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keon\u2010Joo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology Cerebrovascular Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine  Seongnam South Korea"},{"name":"Department of Neurology Korea University Guro Hospital  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong\u2010Moo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurology Uijeongbu Eulji Medical Center, Eulji University  Uijeongbu South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyusik","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Neurology Nowon Eulji Medical Center, Eulji University  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Joo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology Eulji University Hospital, Eulji University  Daejeon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Guk","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology Eulji University Hospital, Eulji University  Daejeon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae\u2010Kwan","family":"Cha","sequence":"additional","affiliation":[{"name":"Department of Neurology Dong\u2010A University Hospital  Busan South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae\u2010Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology Dong\u2010A University Hospital  Busan South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moon\u2010Ku","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Neurology Cerebrovascular Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine  Seongnam South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihoon","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Neurology Cerebrovascular Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine  Seongnam South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2719-3012","authenticated-orcid":false,"given":"Beom Joon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology Cerebrovascular Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine  Seongnam South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai Hwan","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurology Seoul Medical Center  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moo\u2010Seok","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurology Seoul Hospital, Ewha Woman's University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Bok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology Soonchunhyang University Hospital  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology Yeungnam University Hospital  Daegu South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keun\u2010Sik","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Neurology Inje University Ilsan Paik Hospital, Inje University College of Medicine  Goyang South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong\u2010Jin","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Neurology Inje University Ilsan Paik Hospital, Inje University College of Medicine  Goyang South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung\u2010Chul","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology Hallym University Sacred Heart Hospital  Anyang South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung\u2010Ho","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology Hallym University Sacred Heart Hospital  Anyang South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6741-0464","authenticated-orcid":false,"given":"Mi Sun","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Neurology Hallym University Sacred Heart Hospital  Anyang South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon\u2010Tae","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology Chonnam National University Hospital  Gwangju South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8851-2104","authenticated-orcid":false,"given":"Kang\u2010Ho","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Neurology Chonnam National University Hospital  Gwangju South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong\u2010Eog","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology Dongguk University Ilsan Hospital  Goyang South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wi\u2010Sun","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Neurology Dongguk University Ilsan Hospital  Goyang South Korea"},{"name":"Research Center for Artificial Intelligence JLK Corporation  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay Chol","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Neurology Jeju National University Hospital, Jeju National University School of Medicine  Jeju South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jee\u2010Hyun","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Neurology Ulsan University College of Medicine  Ulsan South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wook\u2010Joo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology Ulsan University College of Medicine  Ulsan South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong\u2010Ick","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Neurology Chungbuk University Hospital  Cheongju South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6900-1242","authenticated-orcid":false,"given":"Sung Il","family":"Sohn","sequence":"additional","affiliation":[{"name":"Department of Neurology Keimyung University Dongsan Medical Center  Daegu South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8235-9855","authenticated-orcid":false,"given":"Jeong\u2010Ho","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Neurology Keimyung University Dongsan Medical Center  Daegu South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juneyoung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Korea University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyunghoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Seoul National University Bundang Hospital, Seoul National University College of Medicine  Seongnam South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junghan","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Seoul National University Bundang Hospital, Seoul National University College of Medicine  Seongnam South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon Seol","family":"Bae","sequence":"additional","affiliation":[{"name":"Research Institute of Future Medicine Samsung Medical Center  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Sub","family":"Cheong","sequence":"additional","affiliation":[{"name":"Research Institute for Life Science GW Vitek  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Debette","sequence":"additional","affiliation":[{"name":"University of Bordeaux Bordeaux Population Health Research Center  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0051-1997","authenticated-orcid":false,"given":"Hee\u2010Joon","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Neurology Cerebrovascular Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine  Seongnam South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000229883.72010.e4"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.112.665760"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.28.7.1361"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.20171"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.854240"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12827"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2014.03.017"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.0020"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.5853\/jos.2015.17.1.7"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.534669"},{"key":"e_1_2_8_12_1","first-page":"e2007","article-title":"How common are single gene mutations as a cause for lacunar stroke?","volume":"93","author":"Tan RYY","year":"2019","journal-title":"A targeted gene panel study Neurology"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.5853\/jos.2015.17.1.38"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-146-2-200701160-00148"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.794529"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2015.02.002"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-015-0338-2"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.5469\/neuroint.2019.00150"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2011.10.035"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.705284"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.5853\/jos.2014.16.3.161"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-02397"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.2147\/CIA.S116724"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.116.013148"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.038439"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1159\/000352065"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2016.09.035"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.002477"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.5853\/jos.2018.02705"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurad.2019.04.002"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2020-325838"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2492080357"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.114.008548"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-015-7969-z"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010525"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.112.663708"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2013.08.010"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.119.013808"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.118.002169"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1275"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.118.024712"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.012281"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijs.12146"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-022-01207-6"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-021-01201-x"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.26575","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ana.26575","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.26575","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T12:37:42Z","timestamp":1705495062000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.26575"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,16]]},"references-count":45,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1002\/ana.26575"],"URL":"https:\/\/doi.org\/10.1002\/ana.26575","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,16]]},"assertion":[{"value":"2022-03-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}