Abstract

Objective: Features of cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) caused by NOTCH3 mutations vary between ethnicities and regions. In Taiwan, more than 70% of CADASIL patients carry the mutation hot spot of p.R544C. We investigated the prevalence of NOTCH3 p.R544C mutation in stroke patients in Taiwan. Methods: This prospective, multicenter study recruited acute stroke patients within 10 days of symptom onset. The p.R544C mutation was identified by polymerase chain reaction with confronting two-pair primers and sequencing. Clinical parameters, vascular risk factors, stroke subtypes, and stroke outcomes were analyzed. Results: Of the 1970 stroke patients (mean age 61.1 ± 13.6 years, male 69.5%) included, 1705 (86.5%) had ischemic stroke and 265 (13.5%) had intracerebral hemorrhage. The prevalence of p.R544C in the study population was 2.8% (95% confidence interval [CI] = 2.1–3.5%). The prevalence was highest in patients with small vessel occlusion type of ischemic stroke (5.6%), followed by intracerebral hemorrhage (5.3%), and infarct of undetermined etiology (2.7%), and was low in patients with cardioembolism (0.8%) and large artery atherosclerosis (0.7%). All p.R544C patients with intracerebral hemorrhage were nonlobar hemorrhage. Sibling history of stroke (odds ratio [OR] = 4.50, 95% CI = 1.67–12.14 in ischemic stroke; OR = 6.03, 95% CI = 1.03–35.47 in intracerebral hemorrhage, respectively) and small vessel occlusion (OR, 4.03, 95% CI, 1.26–12.92) were significantly associated with p.R544C. Interpretation: p.R544C NOTCH3 mutation is underdiagnosed in stroke patients in Taiwan, especially in those with small vessel occlusion and sibling history of stroke.

Original languageEnglish
Pages (from-to)121-128
Number of pages8
JournalAnnals of Clinical and Translational Neurology
Volume6
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

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Taiwan
Stroke
Mutation
Cerebral Hemorrhage
CADASIL
Confidence Intervals
Odds Ratio
Siblings
Multicenter Studies
Atherosclerosis
Arteries
Prospective Studies
Hemorrhage
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

Prevalence and clinical characteristics of stroke patients with p.R544C NOTCH3 mutation in Taiwan. / Tang, Sung Chun; Chen, Yih Ru; Chi, Nai Fang; Chen, Chih Hao; Cheng, Yu Wen; Hsieh, Fang I.; Hsieh, Yi Chen; Yeh, Hsu Ling; Sung, Pi Shan; Hu, Chaur Jong; Chern, Chang Ming; Lin, Huey Juan; Lien, Li Ming; Peng, Giia Sheun; Chiou, Hung Yi; Jeng, Jiann Shing.

In: Annals of Clinical and Translational Neurology, Vol. 6, No. 1, 01.01.2019, p. 121-128.

Research output: Contribution to journalArticle

Tang, Sung Chun ; Chen, Yih Ru ; Chi, Nai Fang ; Chen, Chih Hao ; Cheng, Yu Wen ; Hsieh, Fang I. ; Hsieh, Yi Chen ; Yeh, Hsu Ling ; Sung, Pi Shan ; Hu, Chaur Jong ; Chern, Chang Ming ; Lin, Huey Juan ; Lien, Li Ming ; Peng, Giia Sheun ; Chiou, Hung Yi ; Jeng, Jiann Shing. / Prevalence and clinical characteristics of stroke patients with p.R544C NOTCH3 mutation in Taiwan. In: Annals of Clinical and Translational Neurology. 2019 ; Vol. 6, No. 1. pp. 121-128.
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title = "Prevalence and clinical characteristics of stroke patients with p.R544C NOTCH3 mutation in Taiwan",
abstract = "Objective: Features of cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) caused by NOTCH3 mutations vary between ethnicities and regions. In Taiwan, more than 70{\%} of CADASIL patients carry the mutation hot spot of p.R544C. We investigated the prevalence of NOTCH3 p.R544C mutation in stroke patients in Taiwan. Methods: This prospective, multicenter study recruited acute stroke patients within 10 days of symptom onset. The p.R544C mutation was identified by polymerase chain reaction with confronting two-pair primers and sequencing. Clinical parameters, vascular risk factors, stroke subtypes, and stroke outcomes were analyzed. Results: Of the 1970 stroke patients (mean age 61.1 ± 13.6 years, male 69.5{\%}) included, 1705 (86.5{\%}) had ischemic stroke and 265 (13.5{\%}) had intracerebral hemorrhage. The prevalence of p.R544C in the study population was 2.8{\%} (95{\%} confidence interval [CI] = 2.1–3.5{\%}). The prevalence was highest in patients with small vessel occlusion type of ischemic stroke (5.6{\%}), followed by intracerebral hemorrhage (5.3{\%}), and infarct of undetermined etiology (2.7{\%}), and was low in patients with cardioembolism (0.8{\%}) and large artery atherosclerosis (0.7{\%}). All p.R544C patients with intracerebral hemorrhage were nonlobar hemorrhage. Sibling history of stroke (odds ratio [OR] = 4.50, 95{\%} CI = 1.67–12.14 in ischemic stroke; OR = 6.03, 95{\%} CI = 1.03–35.47 in intracerebral hemorrhage, respectively) and small vessel occlusion (OR, 4.03, 95{\%} CI, 1.26–12.92) were significantly associated with p.R544C. Interpretation: p.R544C NOTCH3 mutation is underdiagnosed in stroke patients in Taiwan, especially in those with small vessel occlusion and sibling history of stroke.",
author = "Tang, {Sung Chun} and Chen, {Yih Ru} and Chi, {Nai Fang} and Chen, {Chih Hao} and Cheng, {Yu Wen} and Hsieh, {Fang I.} and Hsieh, {Yi Chen} and Yeh, {Hsu Ling} and Sung, {Pi Shan} and Hu, {Chaur Jong} and Chern, {Chang Ming} and Lin, {Huey Juan} and Lien, {Li Ming} and Peng, {Giia Sheun} and Chiou, {Hung Yi} and Jeng, {Jiann Shing}",
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T1 - Prevalence and clinical characteristics of stroke patients with p.R544C NOTCH3 mutation in Taiwan

AU - Tang, Sung Chun

AU - Chen, Yih Ru

AU - Chi, Nai Fang

AU - Chen, Chih Hao

AU - Cheng, Yu Wen

AU - Hsieh, Fang I.

AU - Hsieh, Yi Chen

AU - Yeh, Hsu Ling

AU - Sung, Pi Shan

AU - Hu, Chaur Jong

AU - Chern, Chang Ming

AU - Lin, Huey Juan

AU - Lien, Li Ming

AU - Peng, Giia Sheun

AU - Chiou, Hung Yi

AU - Jeng, Jiann Shing

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objective: Features of cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) caused by NOTCH3 mutations vary between ethnicities and regions. In Taiwan, more than 70% of CADASIL patients carry the mutation hot spot of p.R544C. We investigated the prevalence of NOTCH3 p.R544C mutation in stroke patients in Taiwan. Methods: This prospective, multicenter study recruited acute stroke patients within 10 days of symptom onset. The p.R544C mutation was identified by polymerase chain reaction with confronting two-pair primers and sequencing. Clinical parameters, vascular risk factors, stroke subtypes, and stroke outcomes were analyzed. Results: Of the 1970 stroke patients (mean age 61.1 ± 13.6 years, male 69.5%) included, 1705 (86.5%) had ischemic stroke and 265 (13.5%) had intracerebral hemorrhage. The prevalence of p.R544C in the study population was 2.8% (95% confidence interval [CI] = 2.1–3.5%). The prevalence was highest in patients with small vessel occlusion type of ischemic stroke (5.6%), followed by intracerebral hemorrhage (5.3%), and infarct of undetermined etiology (2.7%), and was low in patients with cardioembolism (0.8%) and large artery atherosclerosis (0.7%). All p.R544C patients with intracerebral hemorrhage were nonlobar hemorrhage. Sibling history of stroke (odds ratio [OR] = 4.50, 95% CI = 1.67–12.14 in ischemic stroke; OR = 6.03, 95% CI = 1.03–35.47 in intracerebral hemorrhage, respectively) and small vessel occlusion (OR, 4.03, 95% CI, 1.26–12.92) were significantly associated with p.R544C. Interpretation: p.R544C NOTCH3 mutation is underdiagnosed in stroke patients in Taiwan, especially in those with small vessel occlusion and sibling history of stroke.

AB - Objective: Features of cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) caused by NOTCH3 mutations vary between ethnicities and regions. In Taiwan, more than 70% of CADASIL patients carry the mutation hot spot of p.R544C. We investigated the prevalence of NOTCH3 p.R544C mutation in stroke patients in Taiwan. Methods: This prospective, multicenter study recruited acute stroke patients within 10 days of symptom onset. The p.R544C mutation was identified by polymerase chain reaction with confronting two-pair primers and sequencing. Clinical parameters, vascular risk factors, stroke subtypes, and stroke outcomes were analyzed. Results: Of the 1970 stroke patients (mean age 61.1 ± 13.6 years, male 69.5%) included, 1705 (86.5%) had ischemic stroke and 265 (13.5%) had intracerebral hemorrhage. The prevalence of p.R544C in the study population was 2.8% (95% confidence interval [CI] = 2.1–3.5%). The prevalence was highest in patients with small vessel occlusion type of ischemic stroke (5.6%), followed by intracerebral hemorrhage (5.3%), and infarct of undetermined etiology (2.7%), and was low in patients with cardioembolism (0.8%) and large artery atherosclerosis (0.7%). All p.R544C patients with intracerebral hemorrhage were nonlobar hemorrhage. Sibling history of stroke (odds ratio [OR] = 4.50, 95% CI = 1.67–12.14 in ischemic stroke; OR = 6.03, 95% CI = 1.03–35.47 in intracerebral hemorrhage, respectively) and small vessel occlusion (OR, 4.03, 95% CI, 1.26–12.92) were significantly associated with p.R544C. Interpretation: p.R544C NOTCH3 mutation is underdiagnosed in stroke patients in Taiwan, especially in those with small vessel occlusion and sibling history of stroke.

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