Intracerebral large artery disease in Aicardi-Goutieres syndrome implicates SAMHD1 in vascular homeostasis
Intracerebral large artery disease in Aicardi-Goutieres syndrome implicates SAMHD1 in vascular homeostasis
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DOI：
10.1111/j.1469-8749.2010.03727.x
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发表时间：
2010-08-01
影响因子：
3.8
通讯作者：
Crow, Yanick J.
中科院分区：
文献类型：
--
作者：
Ramesh, Venkateswaran;Bernardi, Bruno;Crow, Yanick J.
AimTo描述一个频谱的脑内大动脉疾病Aicardi-Goutieres综合征（AGS）与AGS 5基因SAMHD1.MethodWe使用的临床和放射学描述和分子analysis.Results5个人（三名男性，两名女性）被确定为具有双等位基因突变SAMHD 1和脑动脉病与周围血管受累导致冻疮和缺血性溃疡。脑血管病变主要是闭塞性的三名患者（终末颈动脉闭塞和基底侧支血管，让人联想到烟雾综合征）和动脉瘤在两个。5例患者中有3例发生脑出血，其中2例患者死亡。一名患者的尸检表明，动脉病变是炎症的origin.InterpretationMutations在SAMHD 1与脑血管病变，这是可能有一个炎性病因。在AGS 1至AGS 4突变的患者中没有观察到类似的疾病，这表明SAMHD 1在血管稳态中的特殊作用。我们的报告提出了关于SAMHD 1突变患者管理的重要问题。
AimTo describe a spectrum of intracerebral large artery disease in Aicardi-Goutieres syndrome (AGS) associated with mutations in the AGS5 gene SAMHD1.MethodWe used clinical and radiological description and molecular analysis.ResultsFive individuals (three males, two females) were identified as having biallelic mutations in SAMHD1 and a cerebral arteriopathy in association with peripheral vessel involvement resulting in chilblains and ischaemic ulceration. The cerebral vasculopathy was primarily occlusive in three patients (with terminal carotid occlusion and basal collaterals reminiscent of moyamoya syndrome) and aneurysmal in two. Three of the five patients experienced intracerebral haemorrhage, which was fatal in two individuals. Post-mortem examination of one patient suggested that the arteriopathy was inflammatory in origin.InterpretationMutations in SAMHD1 are associated with a cerebral vasculopathy which is likely to have an inflammatory aetiology. A similar disease has not been observed in patients with mutations in AGS1 to AGS4, suggesting a particular role for SAMHD1 in vascular homeostasis. Our report raises important questions about the management of patients with mutations in SAMHD1.