{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T07:03:31Z","timestamp":1789628611488,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":258,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2024JJ678"],"award-info":[{"award-number":["2024JJ678"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82501748"],"award-info":[{"award-number":["82501748"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Pathogenic variants in\n                      <jats:italic>TAF1<\/jats:italic>\n                      have previously been associated with X\u2010linked intellectual disability and X\u2010linked dystonia\u2010parkinsonism. Epilepsy is observed in approximately 24.4% of affected individuals, ranging from focal seizures to generalized seizures including either tonic\u2010clonic, tonic, myoclonic, atonic or absences. To date, no cases of infantile epileptic spasm syndrome (IESS) have been associated with this neurogenetic condition. In this study, we are aimed at investigating the association between\n                      <jats:italic>TAF1<\/jats:italic>\n                      and IESS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed whole\u2010exome sequencing in two unrelated Chinese patients with IESS. Functional consequences were assessed using in vitro overexpression assays, transcriptome profiling of Neuro\u20102a cells with stable\n                      <jats:italic>TAF1<\/jats:italic>\n                      knockdown, morphological, and electrophysiological analyses in primary mouse cortical neurons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified two novel\n                      <jats:italic>TAF1<\/jats:italic>\n                      missense variants (c.236C &gt; A, p.T79N; c.4771G &gt; A, p.D1591N) in the two patients. Both novel\n                      <jats:italic>TAF1<\/jats:italic>\n                      missense variants led to reduced TAF1 protein expression, suggesting a loss\u2010of\u2010function mechanism. Transcriptome analysis revealed that\n                      <jats:italic>TAF1<\/jats:italic>\n                      deficiency resulted in significant downregulation of key neuronal genes involved in axon guidance and epileptogenesis, including\n                      <jats:italic>Kcnn2<\/jats:italic>\n                      ,\n                      <jats:italic>Kcna4<\/jats:italic>\n                      ,\n                      <jats:italic>Draxin<\/jats:italic>\n                      , and\n                      <jats:italic>Lgi1<\/jats:italic>\n                      . In primary mouse cortical neurons,\n                      <jats:italic>TAF1<\/jats:italic>\n                      knockdown markedly impaired neurite outgrowth and increased neuronal excitability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings establish\n                      <jats:italic>TAF1<\/jats:italic>\n                      missense variants as a novel cause of IESS\u2014a previously unrecognized phenotype\u2014thereby expanding the epileptic phenotype of\n                      <jats:italic>TAF1<\/jats:italic>\n                      \u2010related disorders. Furthermore, we demonstrate that\n                      <jats:italic>TAF1<\/jats:italic>\n                      deficiency contributes to disease pathogenesis by impairing neuronal development and increasing neuronal excitability, likely through the downregulation of\n                      <jats:italic>Kcnn2<\/jats:italic>\n                      ,\n                      <jats:italic>Kcna4<\/jats:italic>\n                      ,\n                      <jats:italic>Draxin<\/jats:italic>\n                      , and\n                      <jats:italic>Lgi1<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/humu\/4104648","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:18:48Z","timestamp":1789625928000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Infantile Epileptic Spasm Syndrome Caused by\n                    <i>TAF1<\/i>\n                    Missense Variants: Expanding the Epileptic Phenotype and Revealing Underlying Impairments in Neuronal Excitability and Development"],"prefix":"10.1155","volume":"2026","author":[{"given":"Hui","family":"Xiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changning","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyuan","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5471-7563","authenticated-orcid":false,"given":"Leilei","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2022.10.014"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.02.011"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.08.014"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/512129"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.11.005"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24003"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-46632-8"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2019.104539"},{"key":"e_1_2_12_9_2","doi-asserted-by":"crossref","unstructured":"MaoL. 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