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

摘要: Aicardi-Goutieres syndrome (AGS) is a rare inborn multisystemic disease, resembling intrauterine viral infection and resulting in psychomotor retardation, spasticity chilblain-like skin lesions. Diagnostic criteria include intracerebral calcifications elevated interferon-alpha pterin levels cerebrospinal fluid (CSF). We report on four adult siblings with unknown neurodegenerative disease presenting cerebrovascular stenoses, stroke glaucoma childhood, two of whom died at the age 40 29 years. Genome-wide homozygosity mapping identified 170 candidate genes embedded common haplotype 8Mb chromosome 20q11-13. Next generation sequencing entire region c.490C>T (p.Arg164X) mutation SAMHD1, gene most recently described AGS, both alleles all affected siblings. Clinical diagnosis AGS was then confirmed by demonstrating cranial computed tomography CSF three them. In patient fibroblasts, lack SAMHD1 protein expression associated increased basal IL8, while stimulated IFNB1 reduced. conclude that stenoses Arg164X extend phenotypic spectrum AGS. The observed vascular changes likely reflect vasculitis caused dysregulated inflammatory stress response. © 2010 Wiley-Liss, Inc.