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Cerebral arterial stenoses and stroke: novel features of Aicardi-Goutières syndrome caused by the Arg164X mutation in SAMHD1 are associated with altered cytokine expression

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Cerebral arterial stenoses and stroke: novel features of Aicardi-Goutières syndrome caused by the Arg164X mutation in SAMHD1 are associated with altered cytokine expression. / Thiele, Holger; du Moulin, Marcel; Barczyk, Katarzyna; George, Christel; Schwindt, Wolfram; Nürnberg, Gudrun; Frosch, Michael; Kurlemann, Gerhard; Roth, Johannes; Nürnberg, Peter; Rutsch, Frank.

In: HUM MUTAT, Vol. 31, No. 11, 11.2010, p. E1836-50.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Thiele, H, du Moulin, M, Barczyk, K, George, C, Schwindt, W, Nürnberg, G, Frosch, M, Kurlemann, G, Roth, J, Nürnberg, P & Rutsch, F 2010, 'Cerebral arterial stenoses and stroke: novel features of Aicardi-Goutières syndrome caused by the Arg164X mutation in SAMHD1 are associated with altered cytokine expression', HUM MUTAT, vol. 31, no. 11, pp. E1836-50. https://doi.org/10.1002/humu.21357

APA

Thiele, H., du Moulin, M., Barczyk, K., George, C., Schwindt, W., Nürnberg, G., Frosch, M., Kurlemann, G., Roth, J., Nürnberg, P., & Rutsch, F. (2010). Cerebral arterial stenoses and stroke: novel features of Aicardi-Goutières syndrome caused by the Arg164X mutation in SAMHD1 are associated with altered cytokine expression. HUM MUTAT, 31(11), E1836-50. https://doi.org/10.1002/humu.21357

Vancouver

Thiele H, du Moulin M, Barczyk K, George C, Schwindt W, Nürnberg G et al. Cerebral arterial stenoses and stroke: novel features of Aicardi-Goutières syndrome caused by the Arg164X mutation in SAMHD1 are associated with altered cytokine expression. HUM MUTAT. 2010 Nov;31(11):E1836-50. https://doi.org/10.1002/humu.21357

Bibtex

@article{335ae48fe9eb489d91d7d3607551072e,
title = "Cerebral arterial stenoses and stroke: novel features of Aicardi-Gouti{\`e}res syndrome caused by the Arg164X mutation in SAMHD1 are associated with altered cytokine expression",
abstract = "Aicardi-Gouti{\`e}res syndrome (AGS) is a rare inborn multisystemic disease, resembling intrauterine viral infection and resulting in psychomotor retardation, spasticity and chilblain-likeskin lesions. Diagnostic criteria include intracerebral calcifications and elevated interferon-alpha and pterin levels in cerebrospinal fluid (CSF). We report on four adult siblings with unknown neurodegenerative disease presenting with cerebrovascular stenoses, stroke and glaucoma in childhood, two of whom died at the age of 40 and 29 years. Genome-wide homozygosity mapping identified 170 candidate genes embedded in a common haplotype of 8Mb on chromosome 20q11-13. Next generation sequencing of the entire region identified the c.490C>T (p.Arg164X) mutationin SAMHD1, a gene most recently described in AGS, on both alleles in all affected siblings.Clinical diagnosis of AGS was then confirmed by demonstrating intracerebral calcifications on cranial computed tomography in all siblings and elevated pterin levels in CSF in three of them. Inpatient fibroblasts, lack of SAMHD1 protein expression was associated with increased basal expression of IL8, while stimulated expression of IFNB1 was reduced. We conclude that cerebrovascular stenoses and stroke associated with the Arg164X mutation in SAMHD1 extend the phenotypic spectrum of AGS. The observed vascular changes most likely reflect a vasculitis caused by dysregulated inflammatory stress response.",
keywords = "Adult, Autoimmune Diseases of the Nervous System, Base Sequence, Cerebral Arterial Diseases, Codon, Nonsense, Consanguinity, Constriction, Pathologic, Cytokines, DNA Mutational Analysis, DNA Primers, Female, Gene Expression, Haplotypes, Homozygote, Humans, Male, Monomeric GTP-Binding Proteins, Nervous System Malformations, Pedigree, Siblings, Stroke, Young Adult, Case Reports, Journal Article, Research Support, Non-U.S. Gov't",
author = "Holger Thiele and {du Moulin}, Marcel and Katarzyna Barczyk and Christel George and Wolfram Schwindt and Gudrun N{\"u}rnberg and Michael Frosch and Gerhard Kurlemann and Johannes Roth and Peter N{\"u}rnberg and Frank Rutsch",
note = "{\textcopyright}2010 Wiley-Liss, Inc.",
year = "2010",
month = nov,
doi = "10.1002/humu.21357",
language = "English",
volume = "31",
pages = "E1836--50",
journal = "HUM MUTAT",
issn = "1059-7794",
publisher = "Wiley-Liss Inc.",
number = "11",

}

RIS

TY - JOUR

T1 - Cerebral arterial stenoses and stroke: novel features of Aicardi-Goutières syndrome caused by the Arg164X mutation in SAMHD1 are associated with altered cytokine expression

AU - Thiele, Holger

AU - du Moulin, Marcel

AU - Barczyk, Katarzyna

AU - George, Christel

AU - Schwindt, Wolfram

AU - Nürnberg, Gudrun

AU - Frosch, Michael

AU - Kurlemann, Gerhard

AU - Roth, Johannes

AU - Nürnberg, Peter

AU - Rutsch, Frank

N1 - ©2010 Wiley-Liss, Inc.

PY - 2010/11

Y1 - 2010/11

N2 - Aicardi-Goutières syndrome (AGS) is a rare inborn multisystemic disease, resembling intrauterine viral infection and resulting in psychomotor retardation, spasticity and chilblain-likeskin lesions. Diagnostic criteria include intracerebral calcifications and elevated interferon-alpha and pterin levels in cerebrospinal fluid (CSF). We report on four adult siblings with unknown neurodegenerative disease presenting with cerebrovascular stenoses, stroke and glaucoma in childhood, two of whom died at the age of 40 and 29 years. Genome-wide homozygosity mapping identified 170 candidate genes embedded in a common haplotype of 8Mb on chromosome 20q11-13. Next generation sequencing of the entire region identified the c.490C>T (p.Arg164X) mutationin SAMHD1, a gene most recently described in AGS, on both alleles in all affected siblings.Clinical diagnosis of AGS was then confirmed by demonstrating intracerebral calcifications on cranial computed tomography in all siblings and elevated pterin levels in CSF in three of them. Inpatient fibroblasts, lack of SAMHD1 protein expression was associated with increased basal expression of IL8, while stimulated expression of IFNB1 was reduced. We conclude that cerebrovascular stenoses and stroke associated with the Arg164X mutation in SAMHD1 extend the phenotypic spectrum of AGS. The observed vascular changes most likely reflect a vasculitis caused by dysregulated inflammatory stress response.

AB - Aicardi-Goutières syndrome (AGS) is a rare inborn multisystemic disease, resembling intrauterine viral infection and resulting in psychomotor retardation, spasticity and chilblain-likeskin lesions. Diagnostic criteria include intracerebral calcifications and elevated interferon-alpha and pterin levels in cerebrospinal fluid (CSF). We report on four adult siblings with unknown neurodegenerative disease presenting with cerebrovascular stenoses, stroke and glaucoma in childhood, two of whom died at the age of 40 and 29 years. Genome-wide homozygosity mapping identified 170 candidate genes embedded in a common haplotype of 8Mb on chromosome 20q11-13. Next generation sequencing of the entire region identified the c.490C>T (p.Arg164X) mutationin SAMHD1, a gene most recently described in AGS, on both alleles in all affected siblings.Clinical diagnosis of AGS was then confirmed by demonstrating intracerebral calcifications on cranial computed tomography in all siblings and elevated pterin levels in CSF in three of them. Inpatient fibroblasts, lack of SAMHD1 protein expression was associated with increased basal expression of IL8, while stimulated expression of IFNB1 was reduced. We conclude that cerebrovascular stenoses and stroke associated with the Arg164X mutation in SAMHD1 extend the phenotypic spectrum of AGS. The observed vascular changes most likely reflect a vasculitis caused by dysregulated inflammatory stress response.

KW - Adult

KW - Autoimmune Diseases of the Nervous System

KW - Base Sequence

KW - Cerebral Arterial Diseases

KW - Codon, Nonsense

KW - Consanguinity

KW - Constriction, Pathologic

KW - Cytokines

KW - DNA Mutational Analysis

KW - DNA Primers

KW - Female

KW - Gene Expression

KW - Haplotypes

KW - Homozygote

KW - Humans

KW - Male

KW - Monomeric GTP-Binding Proteins

KW - Nervous System Malformations

KW - Pedigree

KW - Siblings

KW - Stroke

KW - Young Adult

KW - Case Reports

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1002/humu.21357

DO - 10.1002/humu.21357

M3 - SCORING: Journal article

C2 - 20842748

VL - 31

SP - E1836-50

JO - HUM MUTAT

JF - HUM MUTAT

SN - 1059-7794

IS - 11

ER -