作者
Frank Arne Wollenweber, Patrizia Hanecker, Anna Bayer-Karpinska, Rainer Malik, Hansjörg Bäzner, Fiona Moreton, Keith W Muir, Susanna Müller, Armin Giese, Christian Opherk, Martin Dichgans, Christof Haffner, Marco Duering
发表日期
2015/3
期刊
Stroke
卷号
46
期号
3
页码范围
786-792
出版商
Lippincott Williams & Wilkins
简介
Background and Purpose
Mutations in NOTCH3 cause cerebral autosomal–dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common monogenic cause of stroke and vascular dementia. Misfolding and aggregation of NOTCH3 proteins triggered by cysteine-affecting mutations are considered to be the key disease mechanisms. However, the significance of cysteine-sparing mutations is still debated.
Methods
We studied a family with inherited small vessel disease by standardized medical history, clinical examination, MRI, ultrastructural analysis of skin biopsies, and Sanger sequencing of all NOTCH3 exons. In addition, we performed in vitro characterization of NOTCH3 variants using recombinant protein fragments and a single-particle aggregation assay.
Results
We identified a novel cysteine-sparing NOTCH3 mutation (D80G) in 4 family members, which was absent in a …
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FA Wollenweber, P Hanecker, A Bayer-Karpinska… - Stroke, 2015