{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:11:36Z","timestamp":1788361896902,"version":"build-2803163510"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T00:00:00Z","timestamp":1673395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004332","name":"Seoul National University Hospital","doi-asserted-by":"publisher","award":["0420220720"],"award-info":[{"award-number":["0420220720"]}],"id":[{"id":"10.13039\/501100004332","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Familial cerebral cavernous malformation (FCCM) is an autosomal dominant disease induced by loss\u2010of\u2010function mutations in three CCM genes, <jats:italic>KRIT1<\/jats:italic>, <jats:italic>CCM2<\/jats:italic>, and <jats:italic>PDCD10<\/jats:italic>. However, previous studies paid little attention to analyzing the radiologic features and age\u2010related disease burden according to the genes. Therefore, we retrospectively reviewed the genetic tests of our center's clinical FCCM patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>This study investigated clinical FCCM patients with multiple lesions or a family history of CCMs who underwent the FCCM gene (<jats:italic>KRTI1<\/jats:italic>, <jats:italic>CCM2<\/jats:italic>, and <jats:italic>PDCD10<\/jats:italic>) panel test. The clinical, genetic, and radiologic features were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>Among the patients (<jats:italic>n<\/jats:italic>\u00a0=\u00a034) undergoing the <jats:italic>FCCM<\/jats:italic> gene test, twenty\u2010seven patients had CCM confirmed by brain MRI, and twenty\u2010one patients were considered to have FCCM (cohort 1). In cohort 1, thirteen patients had mutations in the FCCM gene, but eight did not. Cohort 2 comprised cohort 1 and four family members with the same mutation as the probands. Six novel variants in CCM genes were detected (<jats:italic>KRIT1<\/jats:italic> c.22_26del, c.815dup, c.1094_1098del, c.1147\u20102A&gt;G, c.2124dup, and <jats:italic>PDCD10<\/jats:italic> c.150\u2009+\u20091dup). Cohort 1 demonstrated that brainstem lesions were mostly associated with the mutation detection in CCM genes (brainstem, lateral temporal, and parietal lesions vs. lateral temporal and parietal lesions, AUC 0.928 vs. 0.779, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0389). The radiologic severity worsened according to age in the <jats:italic>KRIT1<\/jats:italic> group compared with the <jats:italic>Mutation not detected<\/jats:italic> group (correlation coefficient 0.75 (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) versus 0.53 (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.004)).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The brainstem lesion could be the radiologic marker for FCCM with the mutation detected. The age\u2010related disease burden regarding FCCM according to genetic information was demonstrated.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51728","type":"journal-article","created":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T13:15:48Z","timestamp":1673442948000},"page":"373-383","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Clinicoradiologic data of familial cerebral cavernous malformation with age\u2010related disease burden"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1791-1815","authenticated-orcid":false,"given":"Seondeuk","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Neurology Seoul National University Hospital  Seoul South Korea"},{"name":"Program in Neuroscience Seoul National University College of Medicine  Seoul South Korea"},{"name":"Laboratory for Neurotherapeutics, Center for Medical Innovation Biomedical Research 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Sang","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology Seoul National University Hospital  Seoul South Korea"},{"name":"Program in Neuroscience Seoul National University College of Medicine  Seoul South Korea"},{"name":"Laboratory for Neurotherapeutics, Center for Medical Innovation Biomedical Research Institute, Seoul National University Hospital  Seoul South Korea"},{"name":"Hospital Medicine Center Seoul National University Hospital  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoonhyuk","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Neurology Seoul National University Hospital  Seoul South Korea"},{"name":"Laboratory for Neurotherapeutics, Center for Medical Innovation Biomedical Research Institute, Seoul National University Hospital  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8064-6749","authenticated-orcid":false,"given":"Kyung\u2010Il","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurology Seoul National University Hospital  Seoul South Korea"},{"name":"Program in Neuroscience Seoul National University College of Medicine  Seoul South Korea"},{"name":"Laboratory for Neurotherapeutics, Center for Medical Innovation Biomedical Research Institute, Seoul National University Hospital  Seoul South Korea"},{"name":"Department of Neurology Seoul National University Hospital Healthcare System Gangnam Center  Seoul 152, Teheran\u2010ro, Gangnam\u2010gu Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1908-0699","authenticated-orcid":false,"given":"Sang Kun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology Seoul National University 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