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

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

Research output: Contribution to journalArticle

62 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)725-732
Number of pages8
JournalDevelopmental Medicine and Child Neurology
Volume52
Issue number8
DOIs
Publication statusPublished - Aug 2010

Fingerprint

Aicardi Syndrome
Blood Vessels
Homeostasis
Arteries
Mutation
Chilblains
Moyamoya Disease
Cerebral Hemorrhage
Autopsy
Genes

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience

Cite this

Intracerebral large artery disease in Aicardi-Goutières syndrome implicates SAMHD1 in vascular homeostasis. / 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.

In: Developmental Medicine and Child Neurology, Vol. 52, No. 8, 08.2010, p. 725-732.

Research output: Contribution to journalArticle

Ramesh, V, Bernardi, B, Stafa, A, Garone, C, Franzoni, E, Abinun, M, Mitchell, P, Mitra, D, Friswell, M, Nelson, J, Shalev, SA, Rice, GI, Gornall, H, Szynkiewicz, M, Aymard, F, Ganesan, V, Prendiville, J, Livingston, JH & Crow, YJ 2010, 'Intracerebral large artery disease in Aicardi-Goutières syndrome implicates SAMHD1 in vascular homeostasis', Developmental Medicine and Child Neurology, vol. 52, no. 8, pp. 725-732. https://doi.org/10.1111/j.1469-8749.2010.03727.x
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. / Intracerebral large artery disease in Aicardi-Goutières syndrome implicates SAMHD1 in vascular homeostasis. In: Developmental Medicine and Child Neurology. 2010 ; Vol. 52, No. 8. pp. 725-732.
@article{60fc4090308449a4b34caedd2688c550,
title = "Intracerebral large artery disease in Aicardi-Gouti{\`e}res syndrome implicates SAMHD1 in vascular homeostasis",
abstract = "Aim: To describe a spectrum of intracerebral large artery disease in Aicardi-Gouti{\`e}res 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.",
author = "Venkateswaran Ramesh and Bruno Bernardi and Altin Stafa and Caterina Garone and Emilio Franzoni and Mario Abinun and Patrick Mitchell and Dipayan Mitra and Mark Friswell and John Nelson and Shalev, {Stavit A.} and Rice, {Gillian I.} and Hannah Gornall and Marcin Szynkiewicz and Fran{\cc}ois Aymard and Vijeya Ganesan and Julie Prendiville and Livingston, {John H.} and Crow, {Yanick J.}",
year = "2010",
month = "8",
doi = "10.1111/j.1469-8749.2010.03727.x",
language = "English",
volume = "52",
pages = "725--732",
journal = "Developmental Medicine and Child Neurology",
issn = "0012-1622",
publisher = "Wiley-Blackwell",
number = "8",

}

TY - JOUR

T1 - Intracerebral large artery disease in Aicardi-Goutières syndrome implicates SAMHD1 in vascular homeostasis

AU - Ramesh, Venkateswaran

AU - Bernardi, Bruno

AU - Stafa, Altin

AU - Garone, Caterina

AU - Franzoni, Emilio

AU - Abinun, Mario

AU - Mitchell, Patrick

AU - Mitra, Dipayan

AU - Friswell, Mark

AU - Nelson, John

AU - Shalev, Stavit A.

AU - Rice, Gillian I.

AU - Gornall, Hannah

AU - Szynkiewicz, Marcin

AU - Aymard, François

AU - Ganesan, Vijeya

AU - Prendiville, Julie

AU - Livingston, John H.

AU - Crow, Yanick J.

PY - 2010/8

Y1 - 2010/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77955145461&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955145461&partnerID=8YFLogxK

U2 - 10.1111/j.1469-8749.2010.03727.x

DO - 10.1111/j.1469-8749.2010.03727.x

M3 - Article

C2 - 20653736

AN - SCOPUS:77955145461

VL - 52

SP - 725

EP - 732

JO - Developmental Medicine and Child Neurology

JF - Developmental Medicine and Child Neurology

SN - 0012-1622

IS - 8

ER -