{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T01:16:26Z","timestamp":1777770986194,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      gene variants are associated with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). In this study we aimed to examine the presence of pathogenic\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      variants in individuals with suspected CADASIL on the Greek island of Crete. This represents the first report of CADASIL patients in Crete.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We reviewed the medical records of the University Hospital of Heraklion and identified three patients with the clinical diagnosis of CADASIL. In these patients pathogenic NOTCH3 variants were identified through targeted or whole\u2010exome sequencing (WES).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A novel heterozygous variant in exon 4 of the\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      gene (p.Cys206Trp; NM_000435.3:c.618C&gt;G) was found in a 67\u2010year\u2010old woman who suffered from recurrent ischemic strokes, cognitive impairment, depression, and headache, as well as her son, who presented with headache, anxiety disorder, and insomnia. Brain MRI for both patients revealed white matter disease, including the anterior temporal lobes. The characteristics of this variant (a Cys\u2010related variant in the epidermal growth factor repeats area) support its pathogenicity. We also identified a 72\u2010year\u2010old patient affected by CADASIL and carrying a previously described p.Arg607Cys (NM_000435.3:c.1819C&gt;T)\n                      <jats:italic>NOTCH3<\/jats:italic>\n                      variant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This report extends the geographic and genotypic spectrum of pathogenic NOTCH3 variants and documents the first CADASIL cases on the island of Crete, Greece.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.70789","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T04:13:36Z","timestamp":1758860016000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Study of the\n                    <i>NOTCH3<\/i>\n                    Gene Reveals the First CADASIL Cases in Crete and a Novel Pathogenic Variant"],"prefix":"10.1002","volume":"15","author":[{"given":"Ioannis","family":"Zaganas","sequence":"first","affiliation":[{"name":"Neurology\/Neurogenetics Laboratory, School of Medicine University of Crete  Heraklion Crete Greece"},{"name":"Department of Neurology University Hospital of Heraklion  Heraklion Crete Greece"},{"name":"Department of Neurology, School of Medicine University of Crete  Heraklion Crete Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Tsiverdis","sequence":"additional","affiliation":[{"name":"Neurology\/Neurogenetics Laboratory, School of Medicine University of Crete  Heraklion Crete Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evgenia","family":"Kokosali","sequence":"additional","affiliation":[{"name":"Neurology\/Neurogenetics Laboratory, School of Medicine University of Crete  Heraklion Crete 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