ArticleHuman genomics2016
Targeted next generation sequencing identifies novel NOTCH3 gene mutations in CADASIL diagnostics patients.
Article in Human genomics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Association ofMedicina (Kaunas, Lithuania) · 2019Pooled it
- A NOTCH3 p.Gly1105Cys variant in CADASIL: clinical characterization and an updated overview of exon 20 variants.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- The Spectrum ofGenes · 2025Article
- The protocol for an observational Australian cohort study of CADASIL: The AusCADASIL study.Cerebral circulation - cognition and behavior · 2024Article
- Most common NOTCH3 mutations causing CADASIL or CADASIL-like cerebral small vessel disease: A systematic review.Cerebral circulation - cognition and behavior · 2024Review
- Exonic mutations in cell-cell adhesion may contribute to CADASIL-related CSVD pathology.Human genetics · 2023Article
- Phenotypic variability in 446 CADASIL patients: Impact of NOTCH3 gene mutation location in addition to the effects of age, sex and vascular risk factors.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Investigating a Genetic Link Between Alzheimer's Disease and CADASIL-Related Cerebral Small Vessel Disease.Molecular neurobiology · 2022Article
- Investigation of Mitochondrial Related Variants in a Cerebral Small Vessel Disease Cohort.Molecular neurobiology · 2022Article
- NOTCH3 mutations in a cohort of Portuguese patients within CADASIL spectrum phenotype.Neurogenetics · 2022Article
- A heterozygous mutation inFrontiers in genetics · 2022Article
- Performance comparison: exome sequencing as a single test replacing Sanger sequencing.Molecular genetics and genomics : MGG · 2021Article
- Exploring the Hereditary Nature of Migraine.Neuropsychiatric disease and treatment · 2021Review
- Analysis of neurodegenerative disease-causing genes in dementia with Lewy bodies.Acta neuropathologica communications · 2020Article
- Investigating diagnostic sequencing techniques for CADASIL diagnosis.Human genomics · 2020Article
- Advances in genetics of migraine.The journal of headache and pain · 2019Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic, hereditary, small vessel disease of the brain causing stroke and vascular dementia in adults. CADASIL has previously been shown to be caused by varying mutations in the NOTCH3 gene. The disorder is often misdiagnosed due to its significant clinical heterogeneic manifestation with familial hemiplegic migraine and several ataxia disorders as well as the location of the currently identified causative mutations. The aim of this study was to develop a new, comprehensive and efficient single assay strategy for complete molecular diagnosis of NOTCH3 mutations through the use of a custom next-generation sequencing (NGS) panel for improved routine clinical molecular diagnostic testing.
resultsOur custom NGS panel identified nine genetic variants in NOTCH3 (p.D139V, p.C183R, p.R332C, p.Y465C, p.C597W, p.R607H, p.E813E, p.C977G and p.Y1106C). Six mutations were stereotypical CADASIL mutations leading to an odd number of cysteine residues in one of the 34 NOTCH3 gene epidermal growth factor (EGF)-like repeats, including three new typical cysteine mutations identified in exon 11 (p.C597W; c.1791C>G); exon 18 (p.C977G; c.2929T>G) and exon 20 (p.Y1106C; c.3317A>G). Interestingly, a novel missense mutation in the CACNA1A gene was also identified in one CADASIL patient. All variants identified (novel and known) were further investigated using in silico bioinformatic analyses and confirmed through Sanger sequencing.
conclusionsNGS provides an improved and effective methodology for the diagnosis of CADASIL. The NGS approach reduced time and cost for comprehensive genetic diagnosis, placing genetic diagnostic testing within reach of more patients.
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