Evidence map›Paper›PMID 40999599›Full record

ArticleBrain and behavior2025

Study of the NOTCH3 Gene Reveals the First CADASIL Cases in Crete and a Novel Pathogenic Variant.

Ioannis Zaganas, Ioannis Tsiverdis, Evgenia Kokosali, Ionela Litso, Minas Drakos, Irene Skoula, Alexandros Zabetakis, Lambros Mathioudakis, Vassilios Mastorodemos, Panayiotis Mitsias

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Article in Brain and behavior, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Ioannis ZaganasNeurology/Neurogenetics Laboratory, School of Medicine, University of Crete, Heraklion, Crete, Greece.
Ioannis TsiverdisNeurology/Neurogenetics Laboratory, School of Medicine, University of Crete, Heraklion, Crete, Greece.
Evgenia KokosaliNeurology/Neurogenetics Laboratory, School of Medicine, University of Crete, Heraklion, Crete, Greece.
Ionela LitsoNeurology/Neurogenetics Laboratory, School of Medicine, University of Crete, Heraklion, Crete, Greece.
Minas DrakosNeurology/Neurogenetics Laboratory, School of Medicine, University of Crete, Heraklion, Crete, Greece.ORCID https://orcid.org/0000-0001-7384-1861
Irene SkoulaNeurology/Neurogenetics Laboratory, School of Medicine, University of Crete, Heraklion, Crete, Greece.
Alexandros ZabetakisNeurology/Neurogenetics Laboratory, School of Medicine, University of Crete, Heraklion, Crete, Greece.
Lambros MathioudakisNeurology/Neurogenetics Laboratory, School of Medicine, University of Crete, Heraklion, Crete, Greece.
Vassilios MastorodemosDepartment of Neurology, University Hospital of Heraklion, Heraklion, Crete, Greece.
Panayiotis MitsiasDepartment of Neurology, University Hospital of Heraklion, Heraklion, Crete, Greece.

Funding

Flagship Initiative for Neurodegenerative Diseases Research on the Basis of Precision Medicine 2018SE01300001Project CHAngeing - Connected Hubs in Ageing: Healthy Living to Protect Cerebrovascular Function (grant agreement: 101087071), funded by the European Union's Horizon Europe program (Excellence Hubs Call - Horizon-WIDERA-2022-ACCESS-04-01) 101087071
6 · The paper itself

Abstract

backgroundNOTCH3 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 NOTCH3 variants in individuals with suspected CADASIL on the Greek island of Crete. This represents the first report of CADASIL patients in Crete.

methodsWe 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-exome sequencing (WES).

resultsA novel heterozygous variant in exon 4 of the NOTCH3 gene (p.Cys206Trp; NM_000435.3:c.618C>G) was found in a 67-year-old 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-related variant in the epidermal growth factor repeats area) support its pathogenicity. We also identified a 72-year-old patient affected by CADASIL and carrying a previously described p.Arg607Cys (NM_000435.3:c.1819C>T) NOTCH3 variant.

conclusionsThis report extends the geographic and genotypic spectrum of pathogenic NOTCH3 variants and documents the first CADASIL cases on the island of Crete, Greece.

Indexed as

CADASILReceptor, Notch3AgedExome SequencingFemaleGreeceHumansMaleNOTCH3 protein, humanReceptor, Notch3CADASILdementianeurogeneticsNOTCH3stroke

Identifiers

PMID40999599
PMCPMC12463710

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