{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:42:36Z","timestamp":1790995356382,"version":"4.1.0"},"reference-count":15,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Develop Med Child Neuro"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    A recurrent 68\u2010kb heterozygous duplication of the\n                    <jats:italic>ATAD3<\/jats:italic>\n                    locus has been implicated in a mitochondrial disorder characterized by prenatal or neonatal onset and rapidly fatal course with cardiomyopathy, hyperlactataemia, cataract, and encephalopathy. We analysed the clinical, neuroimaging, and molecular spectrum associated with duplication of the\n                    <jats:italic>ATAD3<\/jats:italic>\n                    gene cluster in nine patients (four males, five females; age range: 3\u2009days\u20133\u2009years, median: 11\u2009days, mean: 7.8\u2009months, SD: 1\u2009year 1\u2009month). Five patients presented with prenatal signs (intrauterine growth restriction in four of nine and cardiac abnormalities in three of nine) leading to medical termination of pregnancy in one case. All live\u2010born children presented with neonatal hypotonia, frequently associated with cardiomyopathy (five of eight), cataract or corneal opacities (five of eight), and hyperlactataemia (six of eight). Two patients carrying distinct duplications exhibited a long survival (&gt;2\u2009years) and presented with major progressive brain atrophy with epileptic encephalopathy. We documented elevated cerebrospinal fluid neopterin in one and increased cerebrospinal fluid alpha\u2010interferon activity in the other. Brain magnetic resonance imaging showed white matter T2 hyperintensity (seven of seven) and temporal cystic leukoencephalopathy (five of seven). Nuclear magnetic resonance spectroscopy showed a lactate peak in five of five patients; brain computed tomography showed basal ganglia calcifications in two of three patients. In this study, we expand the clinical spectrum of\n                    <jats:italic>ATAD3<\/jats:italic>\n                    duplications, including prolonged survival and severe neurological involvement with neuroimaging similarities to Aicardi\u2013Gouti\u00e8res syndrome and more broadly interferonopathy. We suggest a putative common mechanism that involves mitochondrial nucleic acid leakage and interferon response.\n                  <\/jats:p>","DOI":"10.1111\/dmcn.16414","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T05:15:40Z","timestamp":1752642940000},"page":"287-294","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>\n                      <i>ATAD3<\/i>\n                    <\/scp>\n                    duplications bridge mitochondrial diseases and Aicardi\u2013Gouti\u00e8res syndrome"],"prefix":"10.1111","volume":"68","author":[{"given":"Pauline","family":"Plant\u00e9\u2010Bordeneuve","sequence":"first","affiliation":[{"name":"Service de M\u00e9decine G\u00e9nomique des Maladies Rares APHP Centre, H\u00f4pital Necker\u2010Enfants Malades  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire\u2010Marine","family":"B\u00e9rat","sequence":"additional","affiliation":[{"name":"Reference Center for Mitochondrial Disorders Necker Hospital, APHP, Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Hanein","sequence":"additional","affiliation":[{"name":"Bioinformatic Platform Institute of Genetic Diseases, INSERM UMR1163, Institut Imagine, Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyril","family":"Gitiaux","sequence":"additional","affiliation":[{"name":"Paediatric Neurology Department Necker Hospital, APHP Centre, Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9, Imagine Institute, INSERM UMR 1163  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"ATAD3 Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Steffann","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine G\u00e9nomique des Maladies Rares APHP Centre, H\u00f4pital Necker\u2010Enfants Malades  Paris France"},{"name":"Reference Center for Mitochondrial Disorders Necker Hospital, APHP, Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9, Imagine Institute, INSERM UMR 1163  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Desguerre","sequence":"additional","affiliation":[{"name":"Reference Center for Mitochondrial Disorders Necker Hospital, APHP, Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Paediatric Neurology Department Necker Hospital, APHP Centre, Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9, Imagine Institute, INSERM UMR 1163  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"R\u00f6tig","sequence":"additional","affiliation":[{"name":"Reference Center for Mitochondrial Disorders Necker Hospital, APHP, Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9, Imagine Institute, INSERM UMR 1163  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Boddaert","sequence":"additional","affiliation":[{"name":"Reference Center for Mitochondrial Disorders Necker Hospital, APHP, Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9, Imagine Institute, INSERM UMR 1163  Paris France"},{"name":"Paediatric Radiology Department APHP, H\u00f4pital Necker\u2010Enfants Malades, Universit\u00e9 Paris Cit\u00e9, Institut Imagine, INSERM U1163 and U1299  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6657-5040","authenticated-orcid":false,"given":"Giulia","family":"Barcia","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine G\u00e9nomique des Maladies Rares APHP Centre, H\u00f4pital Necker\u2010Enfants Malades  Paris France"},{"name":"Reference Center for Mitochondrial Disorders Necker Hospital, APHP, Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9, Imagine Institute, INSERM UMR 1163  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24362"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.102784"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adp7114"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00007-10"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.08.007"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medj.2020.06.004"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2020.01.007"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0686-8"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.398"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3850"},{"issue":"1","key":"e_1_2_9_12_1","first-page":"1","article-title":"Interferon signature: a new biomarker to follow disease progression in Pearson and Kearns\u2010Sayre syndrome","volume":"42","author":"Martinelli D","year":"2019","journal-title":"J Inherit Metab Dis."},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26880-x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0363-0"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2020-107367"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201560"}],"container-title":["Developmental Medicine &amp; Child 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