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Intracerebral large artery disease in Aicardi–Goutières syndrome implicates SAMHD1 in vascular homeostasis |
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| Authors: | VENKATESWARAN RAMESH BRUNO BERNARDI ALTIN STAFA CATERINA GARONE EMILIO FRANZONI MARIO ABINUN PATRICK MITCHELL DIPAYAN MITRA MARK FRISWELL JOHN NELSON STAVIT A SHALEV GILLIAN I RICE HANNAH GORNALL MARCIN SZYNKIEWICZ FRANÇOIS AYMARD VIJEYA GANESAN JULIE PRENDIVILLE JOHN H LIVINGSTON YANICK J CROW |
| Affiliation: | 1. Department of Paediatric Neurology, Newcastle General Hospital, Newcastle upon Tyne, UK;2. Department of Neuroscience, Paediatric Neuroradiology, Bellaria Hospital, Bologna, Italy;3. Child Neuropsychiatric Unit, S.Orsola‐Malpighi Hospital, University of Bologna, Italy;4. Department of Paediatric Immunology, Newcastle General Hospital, Newcastle upon Tyne, UK;5. Department of Neurosurgery, Newcastle General Hospital, Newcastle upon Tyne, UK;6. Department of Neuroradiology, Newcastle General Hospital, Newcastle upon Tyne, UK;7. Department of Paediatric Rheumatology, Newcastle General Hospital, Newcastle upon Tyne, UK;8. Genetic Services of Western Australia, King Edward Memorial Hospital, Perth, Western Australia, Australia;9. The Genetic Institute, Ha’Emek Medical Center, Afula, and the Rappaport Faculty of Medicine, Technion‐Israel Institute of Technology, Haifa, Israel;10. Genetic Medicine, University of Manchester, Manchester Academic Health Science Centre, Central Manchester Foundation Trust University Hospitals, Manchester, UK;11. Neurosciences Unit, Institute of Child Health, University College London, London, UK;12. Division of Paediatric Dermatology, British Columbia’s Children’s Hospital, Vancouver, Canada;13. Department of Paediatric Neurology, Leeds General Infirmary, UK |
| Abstract: | 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. |
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