Clinical features and spectrum of
 NOTCH3
 variants in Finnish patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Mönkäre, Saana; Kuuluvainen, Liina; Schleutker, Johanna; Myllykangas, Liisa; Pöyhönen, Minna

doi:10.1111/ane.13703

Cited by 6 publications

(4 citation statements)

References 30 publications

(68 reference statements)

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“…Australia is a multicultural society with extensive ethnic diversity. The predominant ancestry is reported to be from the United Kingdom and Europe (51–81 %)[ 42 ] and, therefore the clinical presentation and pedigree of CADASIL is hypothesized to be most similar to individuals from those regions [ 9 , 43 ]. However, there is also a growing Asian and South East Asian population [ 42 ], which may influence the range of clinical presentation of CADASIL[ 44 , 45 ] in Australia.…”

Section: Discussionmentioning

confidence: 99%

“…CADASIL typically presents with multiple small strokes and complex migraines in individuals aged 30–55 years, leading to disturbances in motor and speech function, mood changes, dementia, and often incontinence [ 7 ]. Large-scale studies have indicated the genetic characteristics, and heterogeneity within the clinical features and severity of symptoms of CADASIL [ [8] , [9] , [10] , [11] ]. The clinical features, severity and prognosis of CADASIL may be influenced by the individual's ethnicity [ 12 ], the position of the pathogenic variant within the NOTCH3 gene [ 13 ], or the presence of disease-modifying variants within the genome [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The protocol for an observational Australian cohort study of CADASIL: The AusCADASIL study

Saks,

Bajorek,

Catts

et al. 2024

Cerebral Circulation - Cognition and Behavior

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The protocol for an observational Australian cohort study of CADASIL: The AusCADASIL study

Saks,

Bajorek,

Catts

et al. 2024

Cerebral Circulation - Cognition and Behavior

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“…Until recently, CADASIL was considered a rare disease. Most of the reported large case series were from developed European countries such as France, Italy, and Finland where access to genetic testing was more readily available [Tikka et al, 2009;Mosca et al, 2011;Mönkäre et al, 2022]. As the clinical presentation became more recognized and access to genetic testing improved, the number of reported cases has been increasing worldwide, including in Asia, the Middle East, Australia, South America, and Africa.…”

Section: Discussionmentioning

confidence: 99%

Detecting a Novel NOTCH3 Variant in Patients with Suspected CADASIL: A Single Center Study

Şanli,

Anlaş

2023

Mol Syndromol

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Introduction: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of familial cerebral small vessel disease in adults and is caused by NOTCH3 variants. Clinical manifestations of CADASIL include recurrent ischemic strokes, dementia, migraine or migraineous headaches, epileptic seizures, and psychiatric disorders. The clinical-radiological phenotype of the disease is also highly variable. In this study, we investigated the variability of clinical, radiological, and genetic data in patients analyzed for NOTCH3 variant in our clinic. Methods: We performed clinical and neuropsychological examination, cerebral magnetic resonance imaging (MRI) and Doppler sonography of cerebral arteries in all patients. Next-generation sequencing test was used for detect variants in NOTCH3 gene from all CADASIL patients. Results: By using the next-generation sequencing method, heterozygous c.380C>T pathogenic variant was detected in the 4th exon of the NOTCH3 gene in 3 patients. This is a previously unreported novel variant and resulted in the replacement of the amino acid Proline at 127th position with Leucine. Discussion and Conclusion: The discovery of this novel pathogenic variant region may contribute to the expansion of the clinical and genetic spectrum of diseases associated with NOTCH3, leading to further research and treatment options for this disease in the future.

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“…ICH development seems to be closely related to CMBs; this has been described in a Taiwanese cohort (87.5%) [ 16 ] and in Jeju Island in South Korea (73.3%) [ 17 ]. In contrast, ICH development was only 1% in Finland [ 25 ] and CMBs were present in 31% of CADASIL patients in the Netherlands [ 26 ]. The frequency of CMBs in HS patients was higher than that in IS patients [ 27 ].…”

Section: Genotype and Phenotype Differences Between Asians And Patien...mentioning

confidence: 99%

Genotype and Phenotype Differences in CADASIL from an Asian Perspective

Kim

Bae

Lee

et al. 2022

IJMS

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Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small-vessel disease caused by mutations in the NOTCH3 gene. Classical pathogenic mechanisms are associated with cysteine gain or loss, but recent studies suggest that cysteine-sparing mutations might have a potential role as a pathogen. In comparison with CADASIL patients in Western countries, there are several differences in Asian patients: (1) prevalent locus of NOTCH3 mutations (exons 2–6 [particularly exon 4] vs. exon 11), (2) age at symptom onset, (3) prevalence of cerebral microbleeds and hemorrhagic stroke, (4) clinical symptoms, and (5) severity of white matter hyperintensities and typical involvement of the anterior temporal pole in magnetic resonance imaging. Both ethnicity and founder effects contribute to these differences in the clinical NOTCH3 spectrum in different cohorts. More functional investigations from diverse races are needed to clarify unknown but novel variants of NOTCH3 mutations. This review may broaden the spectrum of NOTCH3 variants from an Asian perspective and draw attention to the hidden pathogenic roles of NOTCH3 variants.

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Clinical features and spectrum of NOTCH3 variants in Finnish patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Cited by 6 publications

References 30 publications

The protocol for an observational Australian cohort study of CADASIL: The AusCADASIL study

The protocol for an observational Australian cohort study of CADASIL: The AusCADASIL study

Detecting a Novel <i>NOTCH3</i> Variant in Patients with Suspected CADASIL: A Single Center Study

Genotype and Phenotype Differences in CADASIL from an Asian Perspective

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