Journal Article

Intracerebral large artery disease in Aicardi–Goutières syndrome implicates SAMHD1 in vascular homeostasis

FRISWELL, MARK, SZYNKIEWICZ, MARCIN, FRANZONI, EMILIO, PRENDIVILLE, JULIE, STAFA, ALTIN, LIVINGSTON, JOHN H, MITCHELL, PATRICK, GORNALL, HANNAH, ABINUN, MARIO, SHALEV, STAVIT A, CROW, YANICK J, GARONE, CATERINA, GANESAN, VIJEYA, MITRA, DIPAYAN, RAMESH, VENKATESWARAN, BERNARDI, BRUNO, NELSON, JOHN, RICE, GILLIAN I, AYMARD, FRANÇOIS

2010

Overview

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.

• Publisher: Blackwell Publishing Ltd,Mac Keith Press
• Subject: Brain / Carotid Stenosis - genetics / Carotid Stenosis - physiopathology / Cerebral Arterial Diseases - genetics / Cerebral Arterial Diseases - physiopathology / Cerebral Palsy / Child / Child, Preschool / Clinical Diagnosis / Developmental Delays / DNA Mutational Analysis / Evidence / Exodeoxyribonucleases / Female / Homeostasis - physiology / Humans / Infant / Learning Problems / Male / Monomeric GTP-Binding Proteins - genetics / Patients / Phosphoproteins / Point Mutation - genetics / Pregnancy / Proteins - genetics / SAM Domain and HD Domain-Containing Protein 1 / Special Schools / Visual Acuity / Visual Impairments