Letter by Rutten et al Regarding Article, "Cysteine-Sparing CADASIL Mutations in NOTCH3 Show Proaggregatory Properties In Vitro".
Letter by Rutten et al Regarding Article, "Cysteine-Sparing CADASIL Mutations in NOTCH3 Show Proaggregatory Properties In Vitro".
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Rutten 等人关于文章“NOTCH3 中保留半胱氨酸的 CADASIL 突变显示体外聚合特性”的信函。
作者：
J. Rutten;S. V. van Duinen;S. L. Lesnik Oberstein
我们怀着极大的兴趣阅读了Wollenweber等人的文章，1提出在伴有皮质下梗死和白质脑病的常染色体显性脑动脉病（CADASIL）的背景下，使用强荧光靶点扫描来确定罕见的NOTCH 3变体的致病性。CADASIL引起的突变通常导致NOTCH3胞外区半胱氨酸残基的数量不均匀。2在绝大多数患者中（>95%），通过检测NOTCH3外显子2至24中的一个半胱氨酸改变错义突变，可以很容易地确认CADASIL的临床诊断。其他导致CADASIL的NOTCH3突变，如小缺失，也诱导半胱氨酸数量变化，支持未配对半胱氨酸在CADASIL发病机制中的基本作用。3因此，在不存在这种半胱氨酸改变突变的情况下，认为CADASIL不太可能发生。当检测到NOTCH3中的非半胱氨酸改变变体时，这些通常被认为是多态性。那里...
We read with great interest the article by Wollenweber et al,1 proposing the use of scanning for intensely fluorescent targets to determine the pathogenicity of rare NOTCH3 variants in the context of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). CADASIL-causing mutations characteristically lead to an uneven number of cysteine residues in the NOTCH3 ectodomain.2 In the vast majority of patients (>95%), a clinical diagnosis of CADASIL can be readily confirmed by the detection of a cysteine altering missense mutation in one of exons 2 to 24 of NOTCH3 . Other CADASIL-causing NOTCH3 mutations, such as small deletions, also induce numeric cysteine changes, supporting a fundamental role for unpaired cysteines in CADASIL pathogenesis.3 Therefore, in the absence of such a cysteine-altering mutation, CADASIL is considered unlikely. When non–cysteine-altering variants in NOTCH3 are detected, these are generally considered polymorphisms. There …