EphrinB2-EphB4-RASA1 信号在人脑血管发育和疾病中的作用。
EphrinB2-EphB4-RASA1 Signaling in Human Cerebrovascular Development and Disease.
机构信息
Department of Genetics, Yale School of Medicine, New Haven CT, USA; Laboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY, USA.
Department of Neurosurgery, Yale School of Medicine, New Haven CT, USA.
出版信息
Trends Mol Med. 2019 Apr;25(4):265-286. doi: 10.1016/j.molmed.2019.01.009. Epub 2019 Feb 25.
Abstract
Recent whole exome sequencing studies in humans have provided novel insight into the importance of the ephrinB2-EphB4-RASA1 signaling axis in cerebrovascular development, corroborating and extending previous work in model systems. Here, we aim to review the human cerebrovascular phenotypes associated with ephrinB2-EphB4-RASA1 mutations, including those recently discovered in Vein of Galen malformation: the most common and severe brain arteriovenous malformation in neonates. We will also discuss emerging paradigms of the molecular and cellular pathophysiology of disease-causing ephrinB2-EphB4-RASA1 mutations, including the potential role of somatic mosaicism. These observations have potential diagnostic and therapeutic implications for patients with rare congenital cerebrovascular diseases and their families.
摘要
最近的人类全外显子组测序研究为脑发育中 EphrinB2-EphB4-RASA1 信号轴的重要性提供了新的见解，这与模型系统中的先前工作相吻合并进一步扩展了该工作。在这里，我们旨在回顾与 EphrinB2-EphB4-RASA1 突变相关的人类脑血管表型，包括最近在静脉窦畸形中发现的那些：这是新生儿中最常见和最严重的脑动静脉畸形。我们还将讨论导致 EphrinB2-EphB4-RASA1 突变的疾病的分子和细胞病理生理学的新兴范例，包括体细胞嵌合现象的潜在作用。这些观察结果对患有罕见先天性脑血管疾病及其家庭的患者具有潜在的诊断和治疗意义。
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