{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T16:12:57Z","timestamp":1779207177519,"version":"3.51.4"},"reference-count":53,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82071511"],"award-info":[{"award-number":["82071511"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32400837"],"award-info":[{"award-number":["32400837"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Jiangsu Provincial Science and Technology Program","award":["SBE2023750299"],"award-info":[{"award-number":["SBE2023750299"]}]},{"DOI":"10.13039\/501100004608","name":"Jiangsu Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["BK20240362"],"award-info":[{"award-number":["BK20240362"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"crossref","award":["2024M762309"],"award-info":[{"award-number":["2024M762309"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Postdoctoral Special Research Fund of The First Affiliated Hospital of Soochow University","award":["202300470011"],"award-info":[{"award-number":["202300470011"]}]},{"name":"Jiangsu Funding Program for Excellent Postdoctoral Talent","award":["2024ZB248"],"award-info":[{"award-number":["2024ZB248"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,15]]},"abstract":"<jats:p>\n                    Skraban-Deardorff syndrome, a rare neurodevelopmental disorder caused by WD repeat domain 26 (\n                    <jats:italic>WDR26<\/jats:italic>\n                    ) haploinsufficiency, is characterized by intellectual disability, seizures, autistic-like behaviors, and craniofacial anomalies. Despite its genetic association with variants disrupting the C-terminal to LisH (CTLH) E3 ubiquitin ligase complex, the molecular mechanisms linking\n                    <jats:italic>WDR26<\/jats:italic>\n                    dysfunction to neurodevelopmental deficits remain unclear. Here, we demonstrate that\n                    <jats:italic>Wdr26<\/jats:italic>\n                    heterozygous-KO mice (\n                    <jats:italic>\n                      Wdr26\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    ) recapitulated core clinical features of the syndrome, including learning and memory impairments, social dysfunction, heightened seizure susceptibility, and motor deficits, alongside rare craniofacial and dental abnormalities. Mechanistically,\n                    <jats:italic>Wdr26<\/jats:italic>\n                    haploinsufficiency stabilized RUNX1 translocation partner 1 (RUNX1T1), a transcriptional coactivator critical for neuronal differentiation, by impairing its ubiquitination and proteasomal degradation, consequently disrupting the level of microtubule-associated protein 2 (MAP2), a key regulator of dendritic architecture and synaptic plasticity. Early intervention in neonatal\n                    <jats:italic>\n                      Wdr26\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice (P0.5) using AAV-shRNA\u2013mediated\n                    <jats:italic>Runx1t1<\/jats:italic>\n                    knockdown reversed MAP2 overexpression and behavioral deficits. Notably, the antipsychotic risperidone ameliorated cognitive and social impairments in\n                    <jats:italic>\n                      Wdr26\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice by upregulating WDR26 levels, suggesting a potential therapeutic avenue. Our findings not only establish the animal model as a robust preclinical tool but also define the WDR26\/RUNX1T1\/MAP2 regulatory axis as pivotal to the syndrome\u2019s pathogenesis, while identifying actionable therapeutic targets.\n                  <\/jats:p>\n                  <jats:p>Skraban-Deardorff syndrome, caused by WDR26 deficiency, impairs protein breakdown, leading to neurodevelopmental issues; reducing Runx1t1 or risperidone treatment alleviates symptoms in mice, highlighting potential therapies.<\/jats:p>","DOI":"10.1172\/jci195537","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T15:52:22Z","timestamp":1779205942000},"source":"Crossref","is-referenced-by-count":0,"title":["Wdr26 insufficiency causes Skraban-Deardorff syndrome\u2013like neurodevelopmental deficits in mice"],"prefix":"10.1172","volume":"136","author":[{"given":"Xingyun","family":"Xu","sequence":"first","affiliation":[{"name":"Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou, China."},{"name":"Institute of Neuroscience, Soochow University, Suzhou, China."},{"name":"Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaohui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Soochow University, Suzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiyao","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Soochow University, Suzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongjie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Soochow University, Suzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuexia","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Soochow University, Suzhou, China."},{"name":"Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhao","family":"Luo","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Soochow University, Suzhou, China."},{"name":"Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Soochow University, Suzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhigang","family":"Miao","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Soochow University, Suzhou, 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