Small Vessel Disease Phenotype Associated With Monoallelic <i>NOTCH3</i> Loss-of-Function Variants
We conclude that monoallelic <i>NOTCH3</i><sup><i>lof</i></sup> variants cause a small vessel disease that (1) remains subclinical in most cases but may be exacerbated by cardiovascular risk factors and aging, and (2) is distinct from CADASIL regarding vessel pathology and disease severity. These findings will guide counseling and management of individuals in whom a <i>NOTCH3</i><sup><i>lof</i></sup> variant is found.
Authors
- Roman I. Koning (ORCID: https://orcid.org/0000-0001-6736-7147)
- Md Manjurul Islam Shourav (ORCID: https://orcid.org/0000-0003-4340-3849)
- Julie W. Rutten (ORCID: https://orcid.org/0000-0003-3250-7263)
- Mark C. Kruit (ORCID: https://orcid.org/0000-0002-4319-834X)
- James F. Meschia (ORCID: https://orcid.org/0000-0002-4475-8142)
- Aat A. Mulder (ORCID: https://orcid.org/0000-0002-4779-099X)
- Saskia A.J. Lesnik Oberstein (ORCID: https://orcid.org/0000-0002-1268-8995)
- Esther Nibbeling (ORCID: https://orcid.org/0000-0001-8818-3232)
- Keith W. Muir (ORCID: https://orcid.org/0000-0001-9535-022X)
- Minne N. Cerfontaine (ORCID: https://orcid.org/0000-0001-9357-270X)
- Remco J. Hack (ORCID: https://orcid.org/0000-0001-9302-5802)
- Andreas Koupparis (ORCID: https://orcid.org/0000-0002-0737-2347)
- Yi‐Chung Lee (ORCID: https://orcid.org/0000-0003-0102-164X)
- Gido Gravesteijn (ORCID: https://orcid.org/0000-0002-2610-8728)
- Nicola Rifino (ORCID: https://orcid.org/0000-0002-0423-8759)
- S. Neilson (ORCID: https://orcid.org/0000-0001-6363-1908)
- Jeroen Vreijling (ORCID: https://orcid.org/0000-0002-4542-3264)
- Josephine S. van Asbeck (ORCID: https://orcid.org/0009-0000-7713-5067)
Institutions
- National Yang Ming Chiao Tung University (TW)
- Leiden University Medical Center (NL)
- Jacksonville College (US)
- Taipei Veterans General Hospital (TW)
- Queen Elizabeth University Hospital (GB)
- Fondazione IRCCS Istituto Neurologico Carlo Besta (IT)
- Cyprus Institute of Neurology and Genetics (CY)
Publication Details
- Journal
- Neurology
- Published
- 2025-08-29
- DOI
- https://doi.org/10.1212/wnl.0000000000214021
- Primary Topic
- Cerebrovascular and genetic disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- ZonMw
- Leids Universitair Medisch Centrum
- Bontius Stichting
- National Science and Technology Council