Premium
Intracerebral large artery disease in Aicardi–Goutières syndrome implicates SAMHD1 in vascular homeostasis
Author(s) -
RAMESH VENKATESWARAN,
BERNARDI BRUNO,
STAFA ALTIN,
GARONE CATERINA,
FRANZONI EMILIO,
ABINUN MARIO,
MITCHELL PATRICK,
MITRA DIPAYAN,
FRISWELL MARK,
NELSON JOHN,
SHALEV STAVIT A,
RICE GILLIAN I,
GORNALL HANNAH,
SZYNKIEWICZ MARCIN,
AYMARD FRANÇOIS,
GANESAN VIJEYA,
PRENDIVILLE JULIE,
LIVINGSTON JOHN H,
CROW YANICK J
Publication year - 2010
Publication title -
developmental medicine and child neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.658
H-Index - 143
eISSN - 1469-8749
pISSN - 0012-1622
DOI - 10.1111/j.1469-8749.2010.03727.x
Subject(s) - medicine , samhd1 , culprit , vascular disease , etiology , pathology , disease , vascular occlusion , stroke (engine) , gene , biology , genetics , mechanical engineering , engineering , reverse transcriptase , rna , myocardial infarction
Aim To describe a spectrum of intracerebral large artery disease in Aicardi–Goutières syndrome (AGS) associated with mutations in the AGS5 gene SAMHD1 . Method We used clinical and radiological description and molecular analysis. Results Five 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. Interpretation Mutations 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 .