We describe a 15-year-old girl with Aicardi-Goutières syndrome due to compound heterozygous pathogenic variants in SAMHD1 (sterile alpha motif domain and HD domain-containing protein 1).
In addition, interrogating truncation mutants of SAMHD1 observed in AGS patients, we map the nucleic-acid-binding domain to residues 164-442, thus overlapping with the HD domain.
Two groups have identified SAMHD1, a protein encoded by an Aicardi-Goutières Syndrome susceptibility gene, as the factor that restricts infection of macrophages and dendritic cells with HIV-1.
AGS is thought to arise from the accumulation of incompletely metabolized endogenous nucleic acid species owing to mutations in nucleic acid-degrading enzymes TREX1 (AGS1), RNase H2 (AGS2, 3 and 4), and SAMHD1 (AGS5).
Resting CD4(+) T cells from healthy donors following SAMHD1 silencing or from a patient with Aicardi-Goutières syndrome homozygous for a nonsense mutation in SAMHD1 were permissive for HIV-1 infection.
We propose that arthropathy with progressive contractures should now be considered part of the spectrum of Aicardi-Goutières syndrome because of SAMHD1 mutations.
We report on a 12-year-old boy with Aicardi-Goutières syndrome and systemic lupus erythematosus (SLE) due to mutations in the SAMHD1 (sterile alpha motif domain and HD domain-containing protein 1) gene, illustrating an emerging pattern of the natural history of Aicardi-Goutières syndrome characterized by neurological disease followed by symptoms of systemic autoimmunity.
We propose that there may be a phenotypic-genotypic correlation in accordance with the type of mutations inherited in the SAMHD1 genotype and suggest that Aicardi-Goutières syndrome may not be a rare disease in the Ashkenazi-Jewish population.
As an important regulator of cell proliferation and a key player in dNTP homeostasis, mutations to SAMHD1 are implicated in hypermutated cancers, and germline mutations are associated with Chronic Lymphocytic Leukaemia and the inflammatory disorder Aicardi-Goutières Syndrome.
SAMHD1 is a protein involved in Aicardi-Goutières syndrome, a genetic encephalopathy with symptoms mimicking congenital viral infection, that has been proposed to act as a negative regulator of the interferon response.
SAMHD1 possesses both dNTPase and RNase activities and mutations in SAMHD1 cause AGS; however, how SAMHD1-deficiency causes the type I interferon response in patients with AGS remains unknown.
Cerebral arterial stenoses and stroke: novel features of Aicardi-Goutières syndrome caused by the Arg164X mutation in SAMHD1 are associated with altered cytokine expression.