{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:54:25Z","timestamp":1790913265683,"version":"4.1.0"},"reference-count":14,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100009438","name":"National Center of Neurology and Psychiatry","doi-asserted-by":"publisher","award":["26FC0201"],"award-info":[{"award-number":["26FC0201"]}],"id":[{"id":"10.13039\/501100009438","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25ek0109760"],"award-info":[{"award-number":["JP25ek0109760"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP26ek0109760"],"award-info":[{"award-number":["JP26ek0109760"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP26ek0109880"],"award-info":[{"award-number":["JP26ek0109880"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25ek0109674"],"award-info":[{"award-number":["JP25ek0109674"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25ek0109617"],"award-info":[{"award-number":["JP25ek0109617"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP24K02230"],"award-info":[{"award-number":["JP24K02230"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP22K15901"],"award-info":[{"award-number":["JP22K15901"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["JP25ek0109617"],"award-info":[{"award-number":["JP25ek0109617"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["JP26ek0109617"],"award-info":[{"award-number":["JP26ek0109617"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pathogenic variants in AGO1 and AGO2, core components of the Argonaute family, have emerged as causes of rare neurodevelopmental disorders characterized by intellectual disability, marked language impairment, behavioral abnormalities, and distinctive craniofacial features. Reported variants cluster at the L1\u2013PAZ boundary, a structurally sensitive region essential for guide\u2010RNA engagement. We describe two unrelated Japanese individuals carrying de novo variants in\n                    <jats:italic>AGO1<\/jats:italic>\n                    (NM_012199.5):c.569T&gt;C p.(Leu190Pro) or\n                    <jats:italic>AGO2<\/jats:italic>\n                    (NM_012154.6):c.544_546del p.(Phe182del), affecting structurally corresponding residues within this boundary. Both individuals exhibited global developmental delay, hypotonia, midface hypoplasia, thin upper lip, elongated facial shape, and reduced cerebral white matter volume, aligning with previously reported AGO1\u2010 and AGO2\u2010related phenotypes. Structural assessment using AlphaFold2\u2010based AGO1 models and the AGO2 crystal structure confirmed positional equivalence of the affected residues, supporting the concept of a shared structural vulnerability across Argonaute paralogs. These observations expand the phenotypic spectrum of Argonaute\u2010related neurodevelopmental disorders in the Japanese population and highlight RNA\u2010regulatory dysfunction as a coherent pathogenic axis. Recognition of this clinical gestalt may assist clinicians in prioritizing AGO1 and AGO2 during genomic evaluation of unexplained neurodevelopmental disorders.\n                  <\/jats:p>","DOI":"10.1111\/cge.70229","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T23:46:11Z","timestamp":1786491971000},"page":"616-621","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Two Japanese Cases Highlighting Structural and Phenotypic Overlap in\n                    <scp>AGO1<\/scp>\n                    \u2010 and\n                    <scp>AGO2<\/scp>\n                    \u2010Related Neurodevelopmental Disorders"],"prefix":"10.1111","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6216-5666","authenticated-orcid":false,"given":"Munetsugu","family":"Hara","sequence":"first","affiliation":[{"name":"Departments of Pediatrics and Child Health Kurume University School of Medicine  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5415-656X","authenticated-orcid":false,"given":"Nobuhiko","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Osaka Women's and Children's Hospital  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5991-7372","authenticated-orcid":false,"given":"Yukihiro","family":"Kitai","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Bobath Memorial Hospital  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4685-8021","authenticated-orcid":false,"given":"Yoriko","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Child Health Kurume University School of Medicine  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yamaguchi Redcross Hospital  Yamaguchi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0731-4446","authenticated-orcid":false,"given":"Kaori","family":"Fukui","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Child Health Kurume University School of Medicine  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2860-2647","authenticated-orcid":false,"given":"Ryuta","family":"Takase","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Child Health Kurume University School of Medicine  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukina","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Graduate School of Medicine Yokohama City University  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Graduate School of Medicine Yokohama City University  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6961-0438","authenticated-orcid":false,"given":"Kumiko","family":"Yanagi","sequence":"additional","affiliation":[{"name":"Department of Genome Medicine National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0281-9610","authenticated-orcid":false,"given":"Tadashi","family":"Kaname","sequence":"additional","affiliation":[{"name":"Department of Genome Medicine National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9846-6500","authenticated-orcid":false,"given":"Naomichi","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Graduate School of Medicine Yokohama City University  Yokohama Japan"},{"name":"Department of Clinical Genetics Yokohama City University Hospital  Yokohama Japan"},{"name":"Department of Rare Disease Genomics Yokohama City University Hospital  Yokohama Japan"},{"name":"Medical Genome Center National Center of Neurology and Psychiatry  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201019572\u20105"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102021\u2010107751"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2010.110"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010021\u201003819\u20102"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1011"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1221551"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1000"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583\u2010025\u201000926\u20101"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2018.09.004"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.05.017"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/oons\/kvac011"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010020\u201000785\u20102"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2011.05.006"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201007773\u20107"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70229","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.70229","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70229","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:13:57Z","timestamp":1790910837000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.70229"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,11]]},"references-count":14,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1111\/cge.70229"],"URL":"https:\/\/doi.org\/10.1111\/cge.70229","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,11]]},"assertion":[{"value":"2026-06-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}