{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:58:04Z","timestamp":1790675884245,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T00:00:00Z","timestamp":1781913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T00:00:00Z","timestamp":1781913600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Ankyrin repeat domain 11 gene (\n                      <jats:italic>ANKRD11<\/jats:italic>\n                      ) is the key disease gene for autosomal dominant KBG syndrome, and a subset of affected individuals develop epilepsy. However, comprehensive characterization of epilepsy\u2010related phenotypes and genotype\u2013phenotype correlations in\n                      <jats:italic>ANKRD11<\/jats:italic>\n                      variant carriers remains limited. We aimed to integrate a single\u2010center cohort with previously reported cases to delineate the epilepsy phenotype spectrum, evaluate genotype\u2013phenotype associations, and provide clinical information for\n                      <jats:italic>ANKRD11<\/jats:italic>\n                      \u2010related epilepsy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Whole exome sequencing was performed in nine unrelated individuals identified at our center. In addition, a systematic search of PubMed (keywords: \u201c\n                      <jats:italic>ANKRD11<\/jats:italic>\n                      \u201d AND \u201cepilepsy\u201d) was performed up to October 2025, and eligible cases were aggregated for pooled analyses of clinical features.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified nine individuals with heterozygous\n                      <jats:italic>ANKRD11<\/jats:italic>\n                      variants at our center; four had epilepsy, and three variants were novel. In silico analyses suggested stronger predicted deleterious effects for missense variants within repression domain (RD; including RD1 and RD2)\u2010related regions, and localization to RD2 may be associated with potential genotype\u2013phenotype correlations. In a pooled cohort of 163 individuals with\n                      <jats:italic>ANKRD11<\/jats:italic>\n                      variants and epilepsy, seizure onset occurred at a median age of 4.0\u2009years (interquartile range\u2009=\u20091.5\u20138.0). Focal and generalized epilepsies were similarly represented, and absence seizures were reported in 22.8%. Brain magnetic resonance imaging (MRI) abnormalities were observed in 45.9% of individuals with available data; 63.2% of patients in the overall cohort achieved seizure freedom, with 36.8% exhibiting drug\u2010resistant epilepsy. Frameshift variants predominated (60.1%), and variants showed domain\u2010specific enrichment, with missense variants clustering in RD2 and truncating variants enriched outside RD2. Individuals with missense variants tended to have later onset, normal MRI, and higher seizure control rates.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      This integrated analysis expands the mutational spectrum of\n                      <jats:italic>ANKRD11<\/jats:italic>\n                      and provides a consolidated genotype\u2013phenotype landscape of\n                      <jats:italic>ANKRD11<\/jats:italic>\n                      \u2010related epilepsy. Variant class and domain\u2010specific clustering patterns, together with differences in clinical profiles and outcomes, support domain\u2010informed variant interpretation and may improve clinical counseling and management for patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70351","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T13:00:32Z","timestamp":1781960432000},"page":"4922-4938","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Insights into\n                    <i>ANKRD11<\/i>\n                    \u2010related epilepsy from 163 people"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2426-6551","authenticated-orcid":false,"given":"Song","family":"Su","sequence":"first","affiliation":[{"name":"Neurology Department Children's Hospital affiliated to Shandong University  Jinan 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Children's Hospital affiliated to Shandong University  Jinan China"},{"name":"Neurology Department Jinan Children's Hospital  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5229-505X","authenticated-orcid":false,"given":"Ying","family":"Ren","sequence":"additional","affiliation":[{"name":"Neurology Department Children's Hospital affiliated to Shandong University  Jinan China"},{"name":"Neurology Department Jinan Children's Hospital  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1531-4445","authenticated-orcid":false,"given":"Wenchao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Neurology Department Children's Hospital affiliated to Shandong University  Jinan China"},{"name":"Neurology Department Jinan Children's Hospital  Jinan 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