• Journal of Medicine and Life Science
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• v.17 no.3
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• pp.65-73
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• 2020

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a single-gene disease of the cerebral small blood vessels caused by mutations in the NOTCH3 gene on chromosome 19. Although CADASIL was known as a rare disease, recent research has suggested that the NOTCH variants could be found frequently even in the general population. The main clinical features included recurrent stroke, migraine, psychiatric symptoms, and progressive cognitive decline. On brain magnetic resonance imaging, patients with CADASIL showed multifocal white matter hyperintensity lesions, lacunar infarcts, microbleeds, and brain atrophy. Among them, lacunar infarcts and brain atrophy are important in predicting the clinical outcomes of patients with CADASIL. In the Jeju National University Hospital, we have diagnosed 213 CADASIL patients from 2004 to 2020. Most NOTCH3 mutations were located in exon 11 (94.4%), and p.Arg544Cys was the most common mutation. The mean age at diagnosis was 61.0±12.8 years. The most common presenting symptoms were ischemic stroke (24.4%), followed by cognitive impairment(15.0%), headache (8.9%), and dizziness(8.0%). Although the exact prevalence of CADASIL in Jeju is still unknown, the disease prevalence could be as high as 1% of the population considering the prevalence reported in Taiwan. Therefore, it is necessary to discover efficient biomarkers and genetic tests that can accurately screen and diagnose patients suspected of having CADASIL in this region. Ultimately, it is urgent to explore the exact pathogenesis of the disease to identify leading substances of treatment potential, and for this, multi-disciplinary research through active support from the Jeju provincial government as well as the national government is essential.

• Journal of Medicine and Life Science
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• v.16 no.3
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• pp.55-59
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• 2019

Cerebral vessels are functionally and structurally specialized to provide adequate blood flow to brain which shows high metabolic rates. Cerebral hemorrhage or ischemic infarction due to cerebrovascular injury or occlusion can cause the immediate brain damage, and if not treated rapidly, can lead to serious or permanent brain damages, and sometimes life-threatening. Unlike these popular cerebrovascular diseases, there are diseases caused by genetic problems. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one of them. CADASIL does not show the high incidence, but it is considered to be significantly affected by regional obstructiveness such as islands and therefore, to be an important genetic disease in Jeju. This paper aims to summarize the possibility of animal model research that can provide preclinical data for CADASIL disease research and to evaluate its applicability in future research plans.

• Journal of Medicine and Life Science
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• v.15 no.2
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• pp.89-94
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• 2018

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is inherited microangiopathy caused by mutations in the Notch3 gene. Typical findings from brain magnetic resonance imaging (MRI) include subcortical lacunes, extensive white matter change and cerebral microbleeds(CMBs). CMBs are indicative of bleeding-prone microangiopathy. Despite some studies investigating the association between lacunes and cognitive dysfunction in CADASIL, few studies have examined the relationship between cognitive dysfunction and CMBs. We sought to assess whether CMBs are associated with cognitive dysfunction in CADASIL. This study enrolled 83 consecutive patients with CADASIL between April 2012 and January 2014. Their degree of cognitive dysfunction was assessed by the Korean version of the CERAD neuropsychological assessment battery, digit span test, and the Stroop test. A 3.0-T MRI was used to obtain T1-weighted, fluid-attenuated inversion recovery, and susceptibility weighted images. In multiple logistic regression analysis, the grade of CMBs influenced tests of memory dysfunction (p=0.003). Three or more lacunes correlated with dysfunction in the executive domain (p=0.013) and attention domain (p=0.005). White matter hyperintensity (WMH) was an independent predictor of executive dysfunction (p=0.001). These findings suggest that in addition to lacunes, CMBs and WMHs may be useful imaging markers to associated with cognitive dysfunction in CADASIL.

• Journal of Genetic Medicine
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• v.19 no.1
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• pp.38-41
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• 2022

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a single-gene disease caused by mutations in the neurogenic locus notch homolog protein 3 (NOTCH3) gene. The spectrum of clinical manifestations is broad, ranging from asymptomatic to typical ischemic stroke, and mainly depends on the location of the mutations. We describe the case of a 76-year-old female without apparent neurological deficits. However, brain magnetic resonance imaging revealed confluent lesions in the white matter. Direct sequencing of the NOTCH3 gene revealed a novel pathogenic mutation, c.811T>A, which results in a mild phenotype. Therefore, this report will expand the current knowledge in regards to the mutations that can cause CADASIL.