{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lepelley A"],"funding":["National Research Agency","MSDAVENIR","European Research Council","European Reference Network on Skin Disorders","European Union’s Horizon 2020","National Institute for Health Research (NIHR)","Rosetrees","Research Foundation Flanders","Marie Curie"],"pagination":["e20201560"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8374862"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["218(10)"],"pubmed_abstract":["Mitochondrial DNA (mtDNA) has been suggested to drive immune system activation, but the induction of interferon signaling by mtDNA has not been demonstrated in a Mendelian mitochondrial disease. We initially ascertained two patients, one with a purely neurological phenotype and one with features suggestive of systemic sclerosis in a syndromic context, and found them both to demonstrate enhanced interferon-stimulated gene (ISG) expression in blood. We determined each to harbor a previously described de novo dominant-negative heterozygous mutation in ATAD3A, encoding ATPase family AAA domain-containing protein 3A (ATAD3A). We identified five further patients with mutations in ATAD3A and recorded up-regulated ISG expression and interferon α protein in four of them. Knockdown of ATAD3A in THP-"],"journal":["The Journal of experimental medicine"],"pubmed_title":["Enhanced cGAS-STING-dependent interferon signaling associated with mutations in ATAD3A."],"pmcid":["PMC8374862"],"funding_grant_id":["RP-2016-07-019","M375-F1","786142","892311","CF2 100018-CD2","ANR-10-IAHU-01","CF2 100018-CD1","1S22716N"],"pubmed_authors":["Buhas D","Wai T","Wouters C","Crow YJ","Waumans L","Fraitag S","Dyment DA","Hully M","Faes F","Carter E","de Lonlay P","Rodero MP","Seabra L","Dhir A","Fremond ML","Callewaert B","Holden S","Suetens K","Rice GI","Tyynismaa H","Chhun S","Grove L","Della Mina E","De Somer L","Lepelley A","Bodemer C","Kurian MA","McMillan HJ","Van Nieuwenhove E","Bader-Meunier B"],"additional_accession":[]},"is_claimable":false,"name":"Enhanced cGAS-STING-dependent interferon signaling associated with mutations in ATAD3A.","description":"Mitochondrial DNA (mtDNA) has been suggested to drive immune system activation, but the induction of interferon signaling by mtDNA has not been demonstrated in a Mendelian mitochondrial disease. We initially ascertained two patients, one with a purely neurological phenotype and one with features suggestive of systemic sclerosis in a syndromic context, and found them both to demonstrate enhanced interferon-stimulated gene (ISG) expression in blood. We determined each to harbor a previously described de novo dominant-negative heterozygous mutation in ATAD3A, encoding ATPase family AAA domain-containing protein 3A (ATAD3A). We identified five further patients with mutations in ATAD3A and recorded up-regulated ISG expression and interferon α protein in four of them. Knockdown of ATAD3A in THP-","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Oct","modification":"2026-06-01T03:05:43.414Z","creation":"2025-04-05T19:57:48.125Z"},"accession":"S-EPMC8374862","cross_references":{"pubmed":["34387651"],"doi":["10.1084/jem.20201560"]}}