Publications by authors named "Minne N Cerfontaine"
Article Synopsis
- NOTCH3cys variants are common and linked to various small vessel diseases, including early-onset stroke and dementia, but there is no comprehensive staging system to assess their severity.
- A cohort study created and validated a simple staging system for NOTCH3-SVD by analyzing data from several international cohorts and the UK Biobank, focusing on the impact of these variants on CVD outcomes and cognition.
- The new system includes 9 disease stages, aiding in understanding the relationship between stages and clinical outcomes like ischemic strokes, cognitive function, and brain damage.
Background And Objectives: Pathogenic variants in are the main cause of hereditary cerebral small vessel disease (SVD). SVD-associated variants have recently been categorized into high risk (HR), moderate risk (MR), or low risk (LR) for developing early-onset severe SVD. The most severe NOTCH3-associated SVD phenotype is also known as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).
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- A new recessive genetic disorder called NIT1-small vessel disease has been identified, caused by variants in the NIT1 gene that lead to loss of function.* -
- Researchers analyzed seven patients using various techniques like exome sequencing and MRI, discovering significant brain abnormalities and movement disorders primarily presenting in mid-adulthood.* -
- The disease is characterized by a specific set of symptoms including dilated perivascular spaces in the basal ganglia and intracerebral hemorrhages, highlighting its unique features among cerebral small vessel diseases.*
Article Synopsis
- Cysteine-altering missense variants in the NOTCH3 protein cause NOTCH3-associated small vessel disease (NOTCH3-SVD), which shows a wide range of severity, including severe conditions like CADASIL and milder cases.
- The study aimed to enhance risk prediction for NOTCH3-SVD by analyzing differences in NOTCH3cys variant frequencies across various EGFr domains, categorizing them into low, medium, or high-risk classifications.
- The findings revealed that certain EGFr domains (1-6, 8, 11, and 26) were associated with a significantly higher stroke risk compared to others, indicating the potential for genotype-based risk stratification in clinical settings.
Background: A retrospective study has shown that EGFr (epidermal growth factor-like repeat) group in the gene is an important cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) disease modifier of age at first stroke and white matter hyperintensity (WMH) volume. No study has yet assessed the effect of other known CADASIL modifiers, that is, cardiovascular risk factors and sex, in the context of EGFr group. In this study, we determined the relative disease-modifying effects of EGFr group, sex and cardiovascular risk factor on disease severity in the first genotype-driven, large prospective CADASIL cohort study, using a comprehensive battery of CADASIL clinical outcomes and neuroimaging markers.
View Article and Find Full Text PDFBackground: To determine whether extremely mild small vessel disease (SVD) phenotypes can occur in variant carriers from Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) pedigrees using clinical, genetic, neuroimaging, and skin biopsy findings.
Methods: Individuals from CADASIL pedigrees fulfilling criteria for extremely mild -associated SVD (mSVD) were selected from the cross-sectional Dutch CADASIL cohort (n=200), enrolled between 2017 and 2020. Brain magnetic resonance imaging were quantitatively assessed for SVD imaging markers.
NOTCH3 variant position is associated with NOTCH3 aggregation load in CADASIL vasculature.
Neuropathol Appl Neurobiol
February 2022
Aims: CADASIL, the most prevalent hereditary cerebral small vessel disease, is caused by cysteine-altering NOTCH3 variants (NOTCH3 ) leading to vascular NOTCH3 protein aggregation. It has recently been shown that variants located in one of NOTCH3 protein epidermal growth-factor like repeat (EGFr) domains 1-6, are associated with a more severe phenotype than variants located in one of the EGFr domains 7-34. The underlying mechanism for this genotype-phenotype correlation is unknown.
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