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Abstract：
Arteriovenous malformations of the brain (bAVMs) are plexuses of pathological arteries and veins that lack a normal capillary system between them. Intracranial hemorrhage (hemorrhagic stroke) is the most frequent clinical manifestation of AVM, leading to lethal outcomes that are especially high among children and young people. Recently, high-throughput genome sequencing methods have made a notable contribution to the research progress in this subject. In particular, whole-exome sequencing (WES) methods allow the identification of novel mutations. However, the genetic mechanism causing AVM is still unclear. Therefore, the aim of this study was to investigate the potential genetic mechanism underlying AVM. We analyzed the WES data of blood and tissue samples of a 30-year-old Central Asian male diagnosed with AVM. We identified 54 polymorphisms in 43 genes. After in-silica overrepresentation enrichment analysis of the polymorphisms, the SIRT1 gene variant (g.67884831C>T) indicated a possible molecular mechanism of bAVM. Further studies are required to evaluate the functional impact of SIRT1 g.67884831C>T, which may warrant further replication and biological investigations related to sporadic bAVM.
摘要：
脑动静脉畸形（bAVM）是病理性动脉和静脉的丛，它们之间缺乏正常的毛细血管系统。颅内出血（出血性中风）是AVM最常见的临床表现，导致儿童和年轻人中特别高的致命后果。最近,高通量基因组测序方法为该课题的研究进展做出了显著贡献。特别是,全外显子组测序(WES)方法允许鉴定新的突变.然而,导致AVM的遗传机制尚不清楚。因此,本研究的目的是探讨AVM潜在的遗传机制.我们分析了一名30岁被诊断为AVM的中亚男性的血液和组织样本的WES数据。我们在43个基因中鉴定了54个多态性。在二氧化硅中过度表达的多态性富集分析后，SIRT1基因变异(g.67884831C>T)提示bAVM可能的分子机制。需要进一步的研究来评估SIRT1g.67884831C>T的功能影响，这可能需要进一步的复制和与散发性bAVM相关的生物学研究。
