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We aimed at determining the frequency of clinically relevant genetic variants (CRGVs) in a cohort of unselected sCeAD patients by targeted next-generation sequencing (NGS) approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We designed a high-throughput sequencing panel to identify variants in 38 candidate genes associated with arterial dissection or aneurysm and screened patients with apparently sporadic sCeAD, consecutively referred to one comprehensive stroke center from August 2020 to December 2025. The frequency of known disease-causing and pertinent variants of uncertain significance (VUS) was calculated. Then, we performed a systematic review of all studies evaluating the prevalence of monogenic disorders among sCeAD patients up to December 2025.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 183 patients (males, 51.3%; mean age, 42.0\u2009\u00b1\u200911.3 years), 2 (1.1%) carried a CeAD-causing variant in COL3A1 (NM_000090.4:c.2959G\u2009&gt;\u2009A:p.Gly987Ser) and ABCC6 (NM_001351800.1:c.3071G\u2009&gt;\u2009A:p.Arg1024Gln), respectively. In addition, we identified 30 (16.4%) VUS in 25 (13.6%) patients. The analysis of 330 patients across 14 studies yielded a prevalence of carriers of disease-causing variants ranging between 0.4% in series of unselected patients and 23.4% in patients with familial history of CeAD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Systematic search for rare disease-causing variants should not be recommended in all sCeAD cases but it should be limited to selected individuals with a high pre-test probability to harbor a monogenic disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10072-026-09308-6","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T03:39:23Z","timestamp":1788320363000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hereditary connective tissue disorders in unselected patients with spontaneous cervical artery dissection: a targeted next generation sequencing approach and systematic review"],"prefix":"10.1007","volume":"47","author":[{"given":"Lorenzo","family":"Corradi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Ferraro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiammetta","family":"Tesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Abrignani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Castellini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilia","family":"Latte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Claudia","family":"Trapasso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Genovese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Giuseppe","family":"Ritelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Cinquina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Clara","family":"Giliani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Magoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Menozzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8629-3315","authenticated-orcid":false,"given":"Alessandro","family":"Pezzini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"9308_CR1","doi-asserted-by":"publisher","first-page":"685","DOI":"10.2147\/VHRM.S362844","volume":"18","author":"Z Keser","year":"2022","unstructured":"Keser Z, Chiang CC, Benson JC, Pezzini A, Lanzino G (2022) Cervical artery dissections: etiopathogenesis and management. 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