Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are 2 monogenic cerebral small vessel diseases sharing several common clinical features including young stroke, migraine, and cognitive dysfunction. The aim of this study was to understand the role of MELAS in patients with CADASIL-like manifestations. We screened 429 unrelated patients with genetically unassigned CADASIL-like syndrome for mitochondrial DNA m.3243A>G mutation. None of them were found to have the mutation. Our finding suggests that m.3243A>G rarely causes CADASIL-like phenotype. It may be not necessary to consider MELAS as a differential diagnosis of CADASIL. Screening m.3243A>G in patients with CADASIL-like phenotype is of limited value.
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| http://dx.doi.org/10.1016/j.neurobiolaging.2020.08.016 | DOI Listing |
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Targeted exonic sequencing identifies novel variants in a cerebral small vessel disease cohort.
Clin Chim Acta
February 2025
Queensland University of Technology (QUT), Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Faculty of Health, 60 Musk Ave., Kelvin Grove, Queensland 4059, Australia. Electronic address:
Background And Aims: Cerebral small vessel diseases (CSVDs) are a set of conditions that affect the small blood vessels in the brain and can cause severe neurological pathologies such as stroke and vascular dementia. The most common monogenic CSVD is cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) which is caused by mutations in NOTCH3. However, only 15-20% of CADASIL cases referred for genetic testing have pathogenic mutations in NOTCH3.
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Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a monogenic disorder caused by mutations in the gene. The main aim of our survey was to determine if there is an association between phenotypes and genotypes across the most common mutations found in CADASIL patients. We systematically searched clinical studies and genomic databases from 1996 to 2023 to first identify the most common mutations responsible for CADASIL.
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Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology (QUT), 60 Musk Ave, Kelvin Grove, QLD, 4059, Australia.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a condition caused by mutations in NOTCH3 and results in a phenotype characterised by recurrent strokes, vascular dementia and migraines. Whilst a genetic basis for the disease is known, the molecular mechanisms underpinning the pathology of CADASIL are still yet to be determined. Studies conducted at the Genomics Research Centre (GRC) have also identified that only 15-23% of individuals clinically suspected of CADASIL have mutations in NOTCH3.
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Neurobiol Aging
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Department of Experimental Neurology, Center for Stroke Research Berlin (CSB), Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. Electronic address:
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and retinal vasculopathy with cerebral leukodystrophy and systemic manifestations (RVCL-S) are the most common forms of rare monogenic early-onset cerebral small vessel disease and share clinical, and, to different extents, neuroradiological and neuropathological features. However, whether CADASIL and RVCL-S overlapping phenotype may be explained by shared genetic risk or causative factors such as TREX1 coding variants remains poorly understood. To investigate this intriguing hypothesis, we used exome sequencing to screen TREX1 protein-coding variability in a large multi-ethnic cohort of 180 early-onset independent familial and apparently sporadic CADASIL-like Caucasian patients from the USA, Portugal, Finland, Serbia and Turkey.
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Genes (Basel)
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Laboratory of Genetics and Genomics of Rare Diseases, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy.
The TREX1 exonuclease degrades DNA to prevent aberrant nucleic-acid sensing through the cGAS-STING pathway, and dominant Aicardi-Goutières Syndrome type 1 (AGS1) represents one of numerous -related autoimmune diseases. Monoallelic mutations were identified in patients showing early-onset cerebrovascular disease, ascribable to small vessel disease, and CADASIL-like neuroimaging. We report the clinical-neuroradiological features of two patients with AGS-like (Patient A) and CADASIL-like (Patient B) phenotypes carrying the heterozygous p.
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