Genotype and Phenotype Differences in CADASIL from an Asian Perspective

Kim, Yerim; Bae, Jong Seok; Lee, Ju-Young; Song, Heesang; Lee, Ju-Hun; Lee, Minwoo; Kim, Chul‐Ho; Lee, Sang-Hwa

doi:10.3390/ijms231911506

Cited by 11 publications

(10 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[ 8 ] Similarly, most of the NOTCH3 variants detected in this study were between exons 2 and 24. However, recent studies have reported that mutations between exons 25 and 33 may also cause CADASIL,[ 13 ] and we detected four variants in exons 25, 31, and 33. Two of these, L1518M and P2249P, were benign and likely benign, respectively, according to ACMG.…”

Section: Discussionmentioning

confidence: 45%

NOTCH3 Variants in Patients with Suspected CADASIL

Görükmez

Topak

et al. 2023

Annals of Indian Academy of Neurology

View full text Add to dashboard Cite

Background: Cerebral autosomal dominant arteriopathy with subcortical infarctions and leukoencephalopathy (CADASIL) is the most common hereditary form of cerebral small vessel disease. It is clinically, radiologically, and genetically heterogeneous and is caused by NOTCH3 mutations. Methods: In this study, we analyzed NOTCH3 in 368 patients with suspected CADASIL using next-generation sequencing. The significant variants detected were reported along with the clinical and radiological features of the patients. Results: Heterozygous NOTCH3 changes, mostly missense mutations, were detected in 44 of the 368 patients (~12%). Conclusions: In this single-center study conducted on a large patient group, 30 different variants were detected, 17 of which were novel. CADASIL, which can result in mortality, has a heterogeneous phenotype among individuals in terms of clinical, demographic, and radiological findings regardless of the NOTCH3 variant.

show abstract

Section: Discussionmentioning

confidence: 45%

NOTCH3 Variants in Patients with Suspected CADASIL

Görükmez

Topak

et al. 2023

Annals of Indian Academy of Neurology

View full text Add to dashboard Cite

show abstract

“…Previous reports have frequently identified NOTCH3 variants in exons 2-6, particularly exon 4 [Almeida et al, 2022;Kim et al, 2022]. In a study conducted in the United Kingdom, evaluating 200 symptomatic individuals, exon 4 variants were reported in 71.4% of the cases [Adib-Samii et al, 2010].…”

Section: Discussionmentioning

confidence: 96%

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

Şanli,

Anlaş

2023

Mol Syndromol

View full text Add to dashboard Cite

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.

show abstract

“…AM, known for its ability to induce vasodilation and lower blood pressure [7] , may theoretically worsen cerebral hypoperfusion and infarcts. The angiogenic properties of AM may raise concerns about an increased risk of cerebral hemorrhage, which is a common manifestation of CADASIL, particularly in East Asian populations [43] . Although our preclinical experiments with mice overexpressing AM in the systemic circulation have shown restoration of CBF without any damaging effects on the brain, the safety of AM in patients should be confirmed through clinical trials.…”

Section: Discussionmentioning

confidence: 99%

A multicenter, single-arm, phase II clinical trial of adrenomedullin in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Washida,

Saito,

Tanaka

et al. 2024

Cerebral Circulation - Cognition and Behavior

View full text Add to dashboard Cite

Genotype and Phenotype Differences in CADASIL from an Asian Perspective

Cited by 11 publications

References 40 publications

NOTCH3 Variants in Patients with Suspected CADASIL

NOTCH3 Variants in Patients with Suspected CADASIL

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

A multicenter, single-arm, phase II clinical trial of adrenomedullin in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Contact Info

Product

Resources

About