Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary vascular disorder causing ischaemic attacks and strokes in middle-aged adults. Though the clinical spectrum includes some typical symptoms, recognition of the disease, especially at an earlier stage, is very difficult because of the highly variable manifestation and incomplete clinical picture. Characteristic brain MRI findings and the presence of pathogenic variants in the NOTCH3 gene are fundamental for CADASIL diagnosis. In this paper, we provide the first comprehensive report on CADASIL patients from Slovakia. Altogether, we identified 23 different pathogenic variants in 35 unrelated families. In our cohort of patients with clinical suspicion of CADASIL, we found a causal genetic defect and confirmed the diagnosis in 10.2% of cases. We present the case reports with up-to-date unpublished NOTCH3 variants and describe their phenotype–genotype correlation: p.(Cys65Phe), p.(Pro86Leu/Ser502Phe), p.(Arg156*), p.(Cys408Arg), p.(Tyr423Cys), p.(Asp1720His), and p.(Asp1893Thrfs*13). The most frequently described location for pathogenic variants was in exon 4, whereas the most common single variant was p.Arg1076Cys in exon 20. Based on the results of our study, we propose a re-evaluation of the criteria for the selection of patients suitable for NOTCH3 gene analysis. We hereby state that the currently used protocol of a high score requirement is not ideal for assessing molecular analysis, and it will be desirable to be less strict in criteria for genetic testing.

伴有皮层下梗死和白质脑病的常染色体显性遗传性脑动脉病 (CADASIL) 是最常见的遗传性血管疾病，可引起中年人缺血发作和中风。尽管临床谱包括一些典型症状，但由于表现高度可变且临床表现不完整，因此很难识别疾病，尤其是在早期阶段。特征性脑部 MRI 结果和NOTCH3致病性变异的存在基因是 CADASIL 诊断的基础。在本文中，我们提供了关于来自斯洛伐克的 CADASIL 患者的第一份综合报告。总之，我们在 35 个不相关的家族中发现了 23 种不同的致病变异。在临床怀疑 CADASIL 的患者队列中，我们发现了致病基因缺陷，并在 10.2% 的病例中确诊。我们提供最新未发表的NOTCH3病例报告变体并描述它们的表型-基因型相关性：p.(Cys65Phe)、p.(Pro86Leu/Ser502Phe)、p.(Arg156*)、p.(Cys408Arg)、p.(Tyr423Cys)、p.(Asp1720His) 和 p. .(Asp1893Thrfs*13)。致病变异最常被描述的位置在外显子 4，而最常见的单一变异是外显子 20 的 p.Arg1076Cys。根据我们的研究结果，我们建议重新评估选择合适患者的标准用于NOTCH3基因分析。我们特此声明，目前使用的高分要求协议对于评估分子分析并不理想，并且希望在基因测试标准方面不那么严格。