Department of Bionano Technology & Gachon Bionano Research Institute, Gachon University, Seongnam-si, Gyeonggi-do 461-701, Korea.
Department of Neurology, Chung-Ang University College of Medicine, Seoul 06973, Korea.
Int J Mol Sci. 2019 Sep 3;20(17):4298. doi: 10.3390/ijms20174298.
Cerebral small vessel diseases (SVD) have been causally correlated with ischemic strokes, leading to cognitive decline and vascular dementia. Neuroimaging and molecular genetic tests could improve diagnostic accuracy in patients with potential SVD. Several types of monogenic, hereditary cerebral SVD have been identified: cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL), hereditary diffuse leukoencephalopathy with spheroids (HDLS), -related disorders, and Fabry disease. These disorders can be distinguished based on their genetics, pathological and imaging findings, clinical manifestation, and diagnosis. Genetic studies of sporadic cerebral SVD have demonstrated a high degree of heritability, particularly among patients with young-onset stroke. Common genetic variants in monogenic disease may contribute to pathological progress in several cerebral SVD subtypes, revealing distinct genetic mechanisms in different subtype of SVD. Hence, genetic molecular analysis should be used as the final gold standard of diagnosis. The purpose of this review was to summarize the recent discoveries made surrounding the genetics of cerebral SVD and their clinical significance, to provide new insights into the pathogenesis of cerebral SVD, and to highlight the possible convergence of disease mechanisms in monogenic and sporadic cerebral SVD.
脑小血管疾病（SVD）与缺血性中风有因果关系，导致认知能力下降和血管性痴呆。神经影像学和分子遗传学检查可以提高潜在 SVD 患者的诊断准确性。已经确定了几种单基因遗传性脑 SVD 类型：伴有皮质下梗死和白质脑病的常染色体隐性脑动脉病（CARASIL）、伴有皮质下梗死和白质脑病的常染色体显性脑动脉病（CADASIL）、伴有中风和白质脑病的组织蛋白酶 A 相关动脉病（CARASAL）、伴有球体的遗传性弥漫性脑白质病变（HDLS）、相关疾病和法布里病。这些疾病可以根据其遗传学、病理学和影像学表现、临床表现和诊断来区分。散发性脑 SVD 的遗传研究表明其具有高度遗传性，尤其是在年轻起病的中风患者中。单基因疾病中的常见遗传变异可能会导致几种脑 SVD 亚型的病理进展，揭示了不同亚型 SVD 中不同的遗传机制。因此，遗传分子分析应作为诊断的最终金标准。本综述的目的是总结脑 SVD 遗传学及其临床意义的最新发现，为脑 SVD 的发病机制提供新的见解，并强调单基因和散发性脑 SVD 中疾病机制的可能趋同。
