{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:44:14Z","timestamp":1788417854582,"version":"build-2803163510"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T00:00:00Z","timestamp":1735344000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T00:00:00Z","timestamp":1735344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI22\/01127"],"award-info":[{"award-number":["PI22\/01127"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI22\/00272\u201d"],"award-info":[{"award-number":["PI22\/00272\u201d"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Rheumatol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Aicardi-Gouti\u00e8res Syndrome is a monogenic type 1 interferonopathy with infantile onset, characterized by a variable degree of neurological damage. Approximately 7% of Aicardi-Gouti\u00e8res Syndrome cases are caused by pathogenic variants in the\n                      <jats:italic>ADAR<\/jats:italic>\n                      gene and are classified as Aicardi-Gouti\u00e8res Syndrome type 6. Here, we present a new homozygous pathogenic variant in the\n                      <jats:italic>ADAR<\/jats:italic>\n                      gene. Currently, Janus Kinase inhibitors have been proposed to treat selected interferonopathies such as Aicardi-Gouti\u00e8res Syndrome, although limited information is available on its use and results in the neonatal presentation of this disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      We present two siblings, a male neonate with congenital petechial rash, severe thrombopenia and generalized hypotonia and his deceased sister who had normal development until 5 months of age, when she suffered acute encephalopathy. We describe the clinical course, complementary examinations and follow-up with early treatment of the newborn with ruxolitinib. The homozygous variant c.2908G\u2009&gt;\u2009A (p.Ala970Thr) in the\n                      <jats:italic>ADAR<\/jats:italic>\n                      gene was found in both siblings, parents were heterozygous carriers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The homozygous variant c.2908G\u2009&gt;\u2009A (p.Ala970Thr) in the\n                      <jats:italic>ADAR<\/jats:italic>\n                      gene causes Aicardi-Gouti\u00e8res Syndrome type 6. Intrafamilial phenotypic spectrum of the disease varies among individuals with the same pathogenic variant. Early initiation of ruxolitinib improved systemic signs but did not prevent the progression of neurological disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12969-024-01036-5","type":"journal-article","created":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T14:20:48Z","timestamp":1735395648000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Aicardi-Gouti\u00e8res syndrome type 6: report of ADAR variant and clinical outcome after ruxolitinib treatment in the neonatal period"],"prefix":"10.1186","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9797-5994","authenticated-orcid":false,"given":"Alba","family":"Gabaldon-Albero","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Martin-Grau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Marti-Masanet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Lopez-Jimenez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Llorens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Beseler-Soto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Martin-Zamora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berta","family":"Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inmaculada","family":"Calvo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Hernandez-Muela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Rosello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Orellana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,28]]},"reference":[{"key":"1036_CR1","unstructured":"Crow YJ. Aicardi-Gouti\u00e8res Syndrome. In: Adam MP, Feldman J, Mirzaa GM editors GeneReviews\u00ae. Seattle (WA): University of Washington, Seattle; June 29, 2005."},{"issue":"5","key":"1036_CR2","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1007\/s11011-021-00716-5","volume":"36","author":"E Mura","year":"2021","unstructured":"Mura E, Masnada S, Antonello C, et al. Ruxolitinib in Aicardi-Gouti\u00e8res syndrome. Metab Brain Dis. 2021;36(5):859\u201363. https:\/\/doi.org\/10.1007\/s11011-021-00716-5.","journal-title":"Metab Brain Dis"},{"issue":"5","key":"1036_CR3","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1136\/annrheumdis-2021-221814","volume":"81","author":"K Cetin Gedik","year":"2022","unstructured":"Cetin Gedik K, Lamot L, Romano M, et al. The 2021 European Alliance of Associations for Rheumatology\/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE\/PRAAS, SAVI and AGS. Ann Rheum Dis. 2022;81(5):601\u201313. https:\/\/doi.org\/10.1136\/annrheumdis-2021-221814.","journal-title":"Ann Rheum Dis"},{"issue":"10","key":"1036_CR4","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1056\/NEJMc2001362","volume":"383","author":"A Vanderver","year":"2020","unstructured":"Vanderver A, Adang L, Gavazzi F, et al. Janus Kinase Inhibition in the Aicardi-Gouti\u00e8res Syndrome. N Engl J Med. 2020;383(10):986\u20139. https:\/\/doi.org\/10.1056\/NEJMc2001362.","journal-title":"N Engl J Med"},{"issue":"1","key":"1036_CR5","doi-asserted-by":"publisher","first-page":"e1665","DOI":"10.1002\/wrna.1665","volume":"13","author":"B Song","year":"2022","unstructured":"Song B, Shiromoto Y, Minakuchi M, Nishikura K. The role of RNA editing enzyme ADAR1 in human disease. Wiley Interdiscip Rev RNA. 2022;13(1):e1665. https:\/\/doi.org\/10.1002\/wrna.1665.","journal-title":"Wiley Interdiscip Rev RNA"},{"key":"1036_CR6","unstructured":"ClinVar. National Library of Medicine (NLM) National Center for Biotechnology Information (NCBI). https:\/\/www.ncbi.nlm.nih.gov\/clinvar\/?term=adar%5Bgene%5D&redir=gene. Accessed November 29th 2023."},{"issue":"2","key":"1036_CR7","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1002\/ajmg.a.36887","volume":"167A","author":"YJ Crow","year":"2015","unstructured":"Crow YJ, Chase DS, Lowenstein Schmidt J, et al. Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. Am J Med Genet A. 2015;167A(2):296\u2013312. https:\/\/doi.org\/10.1002\/ajmg.a.36887.","journal-title":"Am J Med Genet A"},{"issue":"12","key":"1036_CR8","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1016\/S1474-4422(13)70258-8","volume":"12","author":"GI Rice","year":"2013","unstructured":"Rice GI, Forte GM, Szynkiewicz M, et al. Assessment of interferon-related biomarkers in Aicardi-Gouti\u00e8res syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study. Lancet Neurol. 2013;12(12):1159\u201369. https:\/\/doi.org\/10.1016\/S1474-4422(13)70258-8.","journal-title":"Lancet Neurol"},{"issue":"4","key":"1036_CR9","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1089\/jir.2017.0127","volume":"38","author":"H Kim","year":"2018","unstructured":"Kim H, de Jesus AA, Brooks SR, et al. Development of a validated Interferon score using NanoString Technology. J Interferon Cytokine Res. 2018;38(4):171\u201385. https:\/\/doi.org\/10.1089\/jir.2017.0127.","journal-title":"J Interferon Cytokine Res"},{"issue":"2","key":"1036_CR10","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1111\/cge.14340","volume":"104","author":"C Mart\u00edn-Grau","year":"2023","unstructured":"Mart\u00edn-Grau C, Orellana Alonso C, Rosell\u00f3 Piera M, et al. Expanding the phenotype of PIGP deficiency to multiple congenital anomalies-hypotonia-seizures syndrome. Clin Genet. 2023;104(2):245\u201350. https:\/\/doi.org\/10.1111\/cge.14340.","journal-title":"Clin Genet"},{"issue":"3","key":"1036_CR11","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1055\/s-0037-1601449","volume":"48","author":"GI Rice","year":"2017","unstructured":"Rice GI, Kitabayashi N, Barth M, et al. Genetic, phenotypic, and Interferon Biomarker Status in ADAR1-Related neurological disease. Neuropediatrics. 2017;48(3):166\u201384. https:\/\/doi.org\/10.1055\/s-0037-1601449.","journal-title":"Neuropediatrics"},{"issue":"10","key":"1036_CR12","doi-asserted-by":"publisher","first-page":"e00905","DOI":"10.1002\/mgg3.905","volume":"7","author":"P Wang","year":"2019","unstructured":"Wang P, Yu S, Liu J, Zhang D, Kang X. Seven novel mutations of ADAR in multi-ethnic pedigrees with dyschromatosis symmetrica hereditaria in China. Mol Genet Genomic Med. 2019;7(10):e00905. https:\/\/doi.org\/10.1002\/mgg3.905.","journal-title":"Mol Genet Genomic Med"},{"issue":"12","key":"1036_CR13","doi-asserted-by":"publisher","first-page":"e76","DOI":"10.1136\/annrheumdis-2016-210565","volume":"75","author":"V T\u00fcngler","year":"2016","unstructured":"T\u00fcngler V, K\u00f6nig N, G\u00fcnther C, Engel K, Fiehn C, Smitka M, von der Hagen M, Berner R, Lee-Kirsch MA. Response to: \u2018JAK inhibition in STING-associated interferonopathy\u2019 by Crow et al. Ann Rheum Dis. 2016;75(12):e76. https:\/\/doi.org\/10.1136\/annrheumdis-2016-210565.","journal-title":"Ann Rheum Dis"},{"issue":"6","key":"1036_CR14","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1212\/WNL.0000000000004921","volume":"90","author":"K Kothur","year":"2018","unstructured":"Kothur K, Bandodkar S, Chu S, Wienholt L, Johnson A, Barclay P, Brogan PA, Rice GI, Crow YJ, Dale RC. An open-label trial of JAK 1\/2 blockade in progressive IFIH1-associated neuroinflammation. Neurology. 2018;90(6):289\u201391. https:\/\/doi.org\/10.1212\/WNL.0000000000004921.","journal-title":"Neurology"},{"issue":"3","key":"1036_CR15","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1056\/NEJMoa1905633","volume":"382","author":"F Alsohime","year":"2020","unstructured":"Alsohime F, Martin-Fernandez M, Temsah MH, Alabdulhafid M, Le Voyer T, Alghamdi M, Qiu X, Alotaibi N, Alkahtani A, Buta S, Jouanguy E, Al-Eyadhy A, Gruber C, Hasan GM, Bashiri FA, Halwani R, Hassan HH, Al-Muhsen S, Alkhamis N, Alsum Z, Casanova JL, Bustamante J, Bogunovic D, Alangari AA. JAK inhibitor therapy in a child with inherited USP18 Deficiency. N Engl J Med. 2020;382(3):256\u201365. https:\/\/doi.org\/10.1056\/NEJMoa1905633.","journal-title":"N Engl J Med"},{"key":"1036_CR16","doi-asserted-by":"publisher","first-page":"725868","DOI":"10.3389\/fped.2021.725868","volume":"9","author":"M Cattalini","year":"2021","unstructured":"Cattalini M, Galli J, Zunica F, Ferraro RM, Carpanelli M, Orcesi S, Palumbo G, Pinelli L, Giliani S, Fazzi E, Badolato R. Case Report: the JAK-Inhibitor Ruxolitinib Use in Aicardi-Goutieres Syndrome due to ADAR1 mutation. Front Pediatr. 2021;9:725868. https:\/\/doi.org\/10.3389\/fped.2021.725868.","journal-title":"Front Pediatr"},{"key":"1036_CR17","doi-asserted-by":"publisher","first-page":"825367","DOI":"10.3389\/fimmu.2022.825367","volume":"13","author":"W Li","year":"2022","unstructured":"Li W, Wang W, Wang W, Zhong L, Gou L, Wang C, Ma J, Quan M, Jian S, Tang X, Zhang Y, Wang L, Ma M, Song H. Janus Kinase Inhibitors in the treatment of type I interferonopathies: a Case Series from a single Center in China. Front Immunol. 2022;13:825367. https:\/\/doi.org\/10.3389\/fimmu.2022.825367.","journal-title":"Front Immunol"},{"key":"1036_CR18","doi-asserted-by":"publisher","first-page":"837568","DOI":"10.3389\/fped.2022.837568","volume":"10","author":"A Pararajasingam","year":"2022","unstructured":"Pararajasingam A, Bradley RE, Evans J, Lowe A, Goodwin R, Jolles S. Case Report: Generalised Panniculitis as a Post-COVID-19 presentation in Aicardi-Gouti\u00e8res syndrome treated with Ruxolitinib. Front Pediatr. 2022;10:837568. https:\/\/doi.org\/10.3389\/fped.2022.837568.","journal-title":"Front Pediatr"},{"issue":"2","key":"1036_CR19","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.braindev.2021.10.001","volume":"44","author":"HF Jones","year":"2022","unstructured":"Jones HF, Stoll M, Ho G, O\u2019Neill D, Han VX, Paget S, Stewart K, Lewis J, Kothur K, Troedson C, Crow YJ, Dale RC, Mohammad SS. Autosomal dominant ADAR c.3019G\u2009>\u2009A (p.(G1007R)) variant is an important mimic of hereditary spastic paraplegia and cerebral palsy. Brain Dev. 2022;44(2):153\u201360. https:\/\/doi.org\/10.1016\/j.braindev.2021.10.001.","journal-title":"Brain Dev"}],"container-title":["Pediatric Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12969-024-01036-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12969-024-01036-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12969-024-01036-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T15:02:26Z","timestamp":1735398146000},"score":1,"resource":{"primary":{"URL":"https:\/\/ped-rheum.biomedcentral.com\/articles\/10.1186\/s12969-024-01036-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,28]]},"references-count":19,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["1036"],"URL":"https:\/\/doi.org\/10.1186\/s12969-024-01036-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-3854099\/v1","asserted-by":"object"}]},"ISSN":["1546-0096"],"issn-type":[{"value":"1546-0096","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,28]]},"assertion":[{"value":"10 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 November 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 December 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Informed consent was obtained from the parents of the patients described in this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The family has formally consented to the submission of the case report to the journal.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"110"}}