{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nIFIH1 encodes the cytoplasmic RNA helicase MDA5, a key pattern‐recognition receptor that senses long double‐stranded RNA produced during viral infections and rapidly initiates innate antiviral responses. Early studies identified MDA5 as an interferon‐inducible gene in melanoma cells, where it was linked to growth inhibition and apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Subsequent investigations demonstrated that MDA5, together with its family members such as RIG‐I and LGP2, detects viral RNAs and promotes the activation of the IFN‐β promoter."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In addition, studies revealed that certain viral proteins (for example, the V proteins of diverse paramyxoviruses) directly bind to MDA5 and interfere with its ATPase activity and downstream signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, detailed mechanistic work has shown that post‐translational modifications—including K63‐linked ubiquitination and dynamic sumoylation mediated by TRIM38—modulate the conformational state and activity of MDA5, thereby fine‐tuning its antiviral potential."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "12"}]}, {"type": "t", "text": " In the context of host–pathogen interactions, MDA5 is a central mediator of innate immunity that is actively antagonized by viral proteins such as the SARS‐CoV‑2 M protein and HSV US11, and is also implicated in cooperative signaling with related helicases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical antiviral role, genetic studies have firmly established IFIH1 as a susceptibility locus for several autoimmune and inflammatory disorders. Variants in IFIH1 confer altered risk for type 1 diabetes, with rare loss‐of‐function alleles lowering disease risk."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": " Moreover, genome‐wide association studies have implicated IFIH1 in conditions such as psoriasis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": ", systemic lupus erythematosus"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": ", and selective IgA deficiency."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": " In addition, autoantibodies targeting MDA5 are a diagnostic hallmark in subsets of dermatomyositis, and aberrant gain‐of‐function mutations in IFIH1 underlie disorders such as Singleton–Merten syndrome."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "22", "end_ref": "27"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDeficiencies in IFIH1 function have also been linked to impaired antiviral immunity. 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"}, {"type": "b", "children": [{"type": "t", "text": "mda-5: An interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.022637199"}], "href": "https://doi.org/10.1073/pnas.022637199"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11805321"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11805321"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "J Andrejeva, K S Childs, D F Young, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0407639101"}], "href": "https://doi.org/10.1073/pnas.0407639101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15563593"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15563593"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Mitsutoshi Yoneyama, Mika Kikuchi, Kanae Matsumoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.175.5.2851"}], "href": "https://doi.org/10.4049/jimmunol.175.5.2851"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16116171"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16116171"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jean-Patrick Parisien, Darja Bamming, Akihiko Komuro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A shared interface mediates paramyxovirus interference with antiviral RNA helicases MDA5 and LGP2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.00153-09"}], "href": "https://doi.org/10.1128/JVI.00153-09"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19403670"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19403670"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Robert Besch, Hendrik Poeck, Tobias Hohenauer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon-independent apoptosis in human melanoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI37155"}], "href": "https://doi.org/10.1172/JCI37155"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19620789"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19620789"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jesper Melchjorsen, Johanna Rintahaka, Stine Søby, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Early innate recognition of herpes simplex virus in human primary macrophages is mediated via the MDA5/MAVS-dependent and MDA5/MAVS/RNA polymerase III-independent pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.01106-10"}], "href": "https://doi.org/10.1128/JVI.01106-10"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20739519"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20739519"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "A M A Nasirudeen, Hui Hui Wong, Peiling Thien, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RIG-I, MDA5 and TLR3 synergistically play an important role in restriction of dengue virus infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Negl Trop Dis (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pntd.0000926"}], "href": "https://doi.org/10.1371/journal.pntd.0000926"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21245912"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21245912"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Alys Peisley, Cecilie Lin, Bin Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cooperative assembly and dynamic disassembly of MDA5 filaments for viral dsRNA recognition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1113651108"}], "href": "https://doi.org/10.1073/pnas.1113651108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22160685"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22160685"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Xiaomo Jiang, Lisa N Kinch, Chad A Brautigam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitin-induced oligomerization of the RNA sensors RIG-I and MDA5 activates antiviral innate immune response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.immuni.2012.03.022"}], "href": "https://doi.org/10.1016/j.immuni.2012.03.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22705106"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22705106"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Bin Wu, Alys Peisley, Claire Richards, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for dsRNA recognition, filament formation, and antiviral signal activation by MDA5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2012.11.048"}], "href": "https://doi.org/10.1016/j.cell.2012.11.048"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23273991"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23273991"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Simon Runge, Konstantin M J Sparrer, Charlotte Lässig, et al. "}, {"type": "b", "children": [{"type": "t", "text": "In vivo ligands of MDA5 and RIG-I in measles virus-infected cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Pathog (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.ppat.1004081"}], "href": "https://doi.org/10.1371/journal.ppat.1004081"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24743923"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24743923"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Ming-Ming Hu, Chen-Yang Liao, Qing Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Innate immunity to RNA virus is regulated by temporal and reversible sumoylation of RIG-I and MDA5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20161015"}], "href": "https://doi.org/10.1084/jem.20161015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28250012"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28250012"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Sadeem Ahmad, Xin Mu, Fei Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Breaching Self-Tolerance to Alu Duplex RNA Underlies MDA5-Mediated Inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2017.12.016"}], "href": "https://doi.org/10.1016/j.cell.2017.12.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29395326"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29395326"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Yang Zhao, Xiang Ye, William Dunker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RIG-I like receptor sensing of host RNAs facilitates the cell-intrinsic immune response to KSHV infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-07314-7"}], "href": "https://doi.org/10.1038/s41467-018-07314-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30451863"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30451863"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Yi Zheng, Meng-Wei Zhuang, Lulu Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) membrane (M) protein inhibits type I and III interferon production by targeting RIG-I/MDA-5 signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Signal Transduct Target Ther (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41392-020-00438-7"}], "href": "https://doi.org/10.1038/s41392-020-00438-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33372174"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33372174"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Deborah J Smyth, Jason D Cooper, Rebecca Bailey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng1800"}], "href": "https://doi.org/10.1038/ng1800"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16699517"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16699517"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Sergey Nejentsev, Neil Walker, David Riches, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1167728"}], "href": "https://doi.org/10.1126/science.1167728"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19264985"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19264985"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Amy Strange, Francesca Capon, Chris C A Spencer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.694"}], "href": "https://doi.org/10.1038/ng.694"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20953190"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20953190"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Vesela Gateva, Johanna K Sandling, Geoff Hom, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.468"}], "href": "https://doi.org/10.1038/ng.468"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19838195"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19838195"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Deborah S Cunninghame Graham, David L Morris, Tushar R Bhangale, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with systemic lupus erythematosus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1002341"}], "href": "https://doi.org/10.1371/journal.pgen.1002341"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22046141"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22046141"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Ricardo C Ferreira, Qiang Pan-Hammarström, Robert R Graham, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.644"}], "href": "https://doi.org/10.1038/ng.644"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20694011"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20694011"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Lijuan Xu, Nengming Xiao, Feng Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of RIG-I and MDA5-dependent antiviral response by gC1qR at mitochondria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0811029106"}], "href": "https://doi.org/10.1073/pnas.0811029106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19164550"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19164550"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Shinji Sato, Kana Hoshino, Takashi Satoh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNA helicase encoded by melanoma differentiation-associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: Association with rapidly progressive interstitial lung disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arthritis Rheum (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/art.24621"}], "href": "https://doi.org/10.1002/art.24621"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19565506"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19565506"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Qiong Wang, Deepti R Nagarkar, Emily R Bowman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of double-stranded RNA pattern recognition receptors in rhinovirus-induced airway epithelial cell responses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.0901386"}], "href": "https://doi.org/10.4049/jimmunol.0901386"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19890046"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19890046"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Neera S Narang, Livia Casciola-Rosen, Shufeng Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cutaneous ulceration in dermatomyositis: association with anti-melanoma differentiation-associated gene 5 antibodies and interstitial lung disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arthritis Care Res (Hoboken) (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/acr.22498"}], "href": "https://doi.org/10.1002/acr.22498"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25331610"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25331610"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "John H Livingston, Yanick J Crow "}, {"type": "b", "children": [{"type": "t", "text": "Neurologic Phenotypes Associated with Mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, and IFIH1: Aicardi-Goutières Syndrome and Beyond."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropediatrics (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1055/s-0036-1592307"}], "href": "https://doi.org/10.1055/s-0036-1592307"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27643693"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27643693"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Julio E Molineros, Amit K Maiti, Celi Sun, et al. 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