2020 Fiscal Year Final Research Report
Prevalence and atypical clinical characteristics of NOTCH3 mutations among patients admitted for acute lacunar infarctions
| Project/Area Number |
19K21321
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| Project/Area Number (Other) |
18H06219 (2018)
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund (2019)
Single-year Grants (2018) |
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| Review Section |
0902:General internal medicine and related fields
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
Washida Kazuo 国立研究開発法人国立循環器病研究センター, 病院, 医長 (60467488)
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| Project Period (FY) |
2018-08-24 – 2021-03-31
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| Keywords | CADASIL / CADASIL scale-J / NOTCH3 / R75P mutation / lacunar infarction |
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| Outline of Final Research Achievements |
CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is the most common hereditary small vessel disease and reported with frequency of 2-5/100,000. Recently, it has been clarified that some of the patients with NOTCH3 gene mutations show atypical clinical symptoms of CADASIL. Assuming that NOTCH3 gene mutations may be involved in some cases of lacunar infarction, this study was designed to examine the prevalence of NOTCH3 gene mutations in patients who were initially admitted for lacunar infarctions. In patients hospitalized for lacunar infarctions, the prevalence of CADASIL may be higher than previously thought. The NOTCH3 mutation may be underdiagnosed in early-onset lacunar infarctions due to atypical clinical and neuroimaging features of CADASIL. Thus, early detection of underdiagnosed CADASIL patients might improve the prognosis of the patients.
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| Free Research Field |
神経内科
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| Academic Significance and Societal Importance of the Research Achievements |
CADASILはNOTCH3遺伝子変異により生じる代表的な遺伝性脳小血管病である。CADASIL患者では大脳白質病変が徐々に進行し、中年期からラクナ梗塞を繰り返し、徐々に認知症や運動機能障害が進行する。遺伝性脳小血管病では最も頻度の高い疾患で、欧州では10万人あたり4-15人の患者が存在するとされている。しかしながら近年、NOTCH3遺伝子変異が示された症例でも CADASILに典型的な臨床徴候を示さない例が存在することが明らかになってきた。本研究の結果、CADASILが予想以上にラクナ梗塞発症に関与している可能性が示唆された。
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