Prevalence and clinical characteristics of stroke patients with p.R544C NOTCH3 mutation in Taiwan

Sung Chun Tang, Yih Ru Chen, Nai Fang Chi, Chih Hao Chen, Yu Wen Cheng, Fang I. Hsieh, Yi Chen Hsieh, Hsu Ling Yeh, Pi-Shan Sung, Chaur Jong Hu, Chang Ming Chern, Huey Juan Lin, Li Ming Lien, Giia Sheun Peng, Hung Yi Chiou, Jiann Shing Jeng

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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 - 2019 Jan 1

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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

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Neurology

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Tang, S. C., Chen, Y. R., Chi, N. F., Chen, C. H., Cheng, Y. W., Hsieh, F. I., ... Jeng, J. S. (2019). Prevalence and clinical characteristics of stroke patients with p.R544C NOTCH3 mutation in Taiwan. Annals of Clinical and Translational Neurology, 6(1), 121-128. https://doi.org/10.1002/acn3.690
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 Pi-Shan Sung 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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pages = "121--128",
journal = "Annals of Clinical and Translational Neurology",
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Tang, SC, Chen, YR, Chi, NF, Chen, CH, Cheng, YW, Hsieh, FI, Hsieh, YC, Yeh, HL, Sung, P-S, Hu, CJ, Chern, CM, Lin, HJ, Lien, LM, Peng, GS, Chiou, HY & Jeng, JS 2019, 'Prevalence and clinical characteristics of stroke patients with p.R544C NOTCH3 mutation in Taiwan', Annals of Clinical and Translational Neurology, vol. 6, no. 1, pp. 121-128. https://doi.org/10.1002/acn3.690

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

TY - JOUR

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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