{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:26:46Z","timestamp":1786976806606,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T00:00:00Z","timestamp":1719187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["23ek0109549"],"award-info":[{"award-number":["23ek0109549"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy of unknown etiology. The underlying mechanisms are highly heterogeneous, often including genetic backgrounds. Variants of\n                    <jats:italic>LARS1<\/jats:italic>\n                    , encoding the leucyl\u2010tRNA synthetase 1, are responsible for infantile liver failure syndrome 1. We describe two siblings with ANE caused by compound heterozygous variants of\n                    <jats:italic>LARS1<\/jats:italic>\n                    . Patient 1 was a 17\u2010month\u2010old girl. She presented with generalized seizure and liver dysfunction due to influenza type A infection. Brain magnetic resonance imaging on day 4 of onset showed diffuse high\u2010intensity signals consistent with ANE. She died on day 10. Patient 2, a younger male sibling of patient 1, had mild to moderate developmental delay and growth failure at the age of 18\u2009months. He showed a markedly elevated level of transaminases triggered by infection with human herpesvirus 6. On day 4 of onset, he had generalized seizures. Brain computed tomography showed a diffuse symmetrical hypodensity consistent with ANE. He died on day 7. Whole exome sequencing identified the compound heterozygous variants in\n                    <jats:italic>LARS1<\/jats:italic>\n                    (NM_020117.11) as c.83_88delinsAATGGGATA, p.(Arg28_Phe30delinsLysTryAspIle) and c.1283C&gt;T, p.(Pro428Leu) in both siblings. The severe neurologic phenotype, found in our patients, reflects the complicated pathogenesis of\n                    <jats:italic>LARS1<\/jats:italic>\n                    \u2010related disorder.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.63803","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T08:54:18Z","timestamp":1719219258000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Two siblings with acute necrotizing encephalopathy associated with variants of\n                    <scp>\n                      <i>LARS1<\/i>\n                    <\/scp>"],"prefix":"10.1002","volume":"194","author":[{"given":"Takeshi","family":"Uehara","sequence":"first","affiliation":[{"name":"Division of Medical Genetics Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eijun","family":"Seki","sequence":"additional","affiliation":[{"name":"Department of Neurology Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Nonoda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kitasato University School of Medicine  Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Kumaki","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Tsuyusaki","sequence":"additional","affiliation":[{"name":"Department of Neurology Kanagawa Children's Medical Center  Yokohama 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