title: Intracerebral large artery disease in Aicardi-Goutières syndrome implicates SAMHD1 in vascular homeostasis.
abstract: OBJECTIVE
  To describe a spectrum of intracerebral large artery disease in Aicardi-Goutières syndrome (AGS) associated with mutations in the AGS5 gene SAMHD1.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Paediatric Neurology, Newcastle General Hospital, Newcastle upon Tyne, UK.
authors.forename: Venkateswaran
authors.initials: V
authors.lastname: Ramesh
authors.forename: Bruno
authors.initials: B
authors.lastname: Bernardi
authors.forename: Altin
authors.initials: A
authors.lastname: Stafa
authors.forename: Caterina
authors.initials: C
authors.lastname: Garone
authors.forename: Emilio
authors.initials: E
authors.lastname: Franzoni
authors.forename: Mario
authors.initials: M
authors.lastname: Abinun
authors.forename: Patrick
authors.initials: P
authors.lastname: Mitchell
authors.forename: Dipayan
authors.initials: D
authors.lastname: Mitra
authors.forename: Mark
authors.initials: M
authors.lastname: Friswell
authors.forename: John
authors.initials: J
authors.lastname: Nelson
authors.forename: Stavit A
authors.initials: SA
authors.lastname: Shalev
authors.forename: Gillian I
authors.initials: GI
authors.lastname: Rice
authors.forename: Hannah
authors.initials: H
authors.lastname: Gornall
authors.forename: Marcin
authors.initials: M
authors.lastname: Szynkiewicz
authors.forename: François
authors.initials: F
authors.lastname: Aymard
authors.forename: Vijeya
authors.initials: V
authors.lastname: Ganesan
authors.forename: Julie
authors.initials: J
authors.lastname: Prendiville
authors.forename: John H
authors.initials: JH
authors.lastname: Livingston
authors.forename: Yanick J
authors.initials: YJ
authors.lastname: Crow
mesh_terms: D016893:Carotid Stenosis / Q000235:genetics / Q000503:physiopathology; D002539:Cerebral Arterial Diseases / Q000235:genetics* / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005090:Exodeoxyribonucleases; D005260:Female; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007223:Infant; D008297:Male; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics*; D010750:Phosphoproteins; D017354:Point Mutation / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D000076106:SAM Domain and HD Domain-Containing Protein 1
chemical_list: D010750:Phosphoproteins; D011506:Proteins; D005090:Exodeoxyribonucleases; C429526:three prime repair exonuclease 1; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins