Division of Genetics, Department of Pediatrics, West Virginia University Medicine, One Medical Center Drive, Morgantown, WV, 26506, USA.
Mol Biol Rep. 2024 Aug 1;51(1):883. doi: 10.1007/s11033-024-09820-y.
Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke. Acquired and inherited prothrombotic conditions are the most common risk factors for CVST. Sometimes, an etiology is not found. Wide utilization of next generation sequencing technologies in clinical practice may lead to identification of risk factors other than those classically associated with CVST.
This retrospective clinical-laboratory observational study has a reference patient who presented with CVST as an adolescent. Work up for prothrombotic conditions showed high homocysteine level secondary to homozygosity for a common polymorphism, c.677 C > T in the methylenetetrahydrofolate reductase (MTHFR) gene. His older unaffected brother has a similar MTHFR genotype and high homocysteine. The whole exome sequencing revealed a likely pathogenic variant in the sodium voltage gated channel, alpha subunit 1(SCN1A) gene.
CVST is a multifactorial disease. Prothrombotic conditions are the most common risk factors for CVST. High homocysteine due to the common MTHFR polymorphisms was previously attributed to various thrombotic conditions including CVST. Although high homocysteine due to MTHFR polymorphism may be a contributing factor, additional risk factors such as blood flow abnormalities during SCN1A related seizures may be needed for thrombosis.
脑静脉窦血栓形成（CVST）是一种罕见的中风病因。获得性和遗传性血栓形成倾向是 CVST 最常见的危险因素。有时，无法确定病因。下一代测序技术在临床实践中的广泛应用可能会发现除了与 CVST 经典相关的危险因素以外的其他危险因素。
本回顾性临床-实验室观察性研究以一名青少年 CVST 患者为参考患者。对血栓形成倾向的检查显示同型半胱氨酸水平升高，原因是亚甲基四氢叶酸还原酶（MTHFR）基因 c.677C > T 的常见多态性导致同型半胱氨酸。他年长且未受影响的兄弟也具有类似的 MTHFR 基因型和高同型半胱氨酸。全外显子组测序显示电压门控钠离子通道，α亚基 1（SCN1A）基因中存在可能的致病性变异。
CVST 是一种多因素疾病。血栓形成倾向是 CVST 最常见的危险因素。先前由于常见的 MTHFR 多态性导致的高同型半胱氨酸被归因于各种血栓形成情况，包括 CVST。尽管由于 MTHFR 多态性导致的高同型半胱氨酸可能是一个促成因素，但在 SCN1A 相关癫痫发作期间血流异常等其他危险因素可能也需要导致血栓形成。
