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This study aims to explore the relationship between\n                      <jats:italic>ZFHX3<\/jats:italic>\n                      variants and 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 a cohort of 378 patients with partial (focal) epilepsy. A\n                      <jats:italic>Drosophila Zfh2<\/jats:italic>\n                      knockdown model was used to validate the association between\n                      <jats:italic>ZFHX3<\/jats:italic>\n                      and epilepsy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compound heterozygous\n                      <jats:italic>ZFHX3<\/jats:italic>\n                      variants were identified in eight unrelated cases. The burden of\n                      <jats:italic>ZFHX3<\/jats:italic>\n                      variants was significantly higher in the case cohort, shown by multiple\/specific statistical analyses. In\n                      <jats:italic>Zfh2<\/jats:italic>\n                      knockdown flies, the incidence and duration of seizure-like behaviour were significantly greater than those in the controls. The\n                      <jats:italic>Zfh2<\/jats:italic>\n                      knockdown flies exhibited more firing in excitatory neurons. All patients presented partial seizures. The five patients with variants in the C-terminus\/N-terminus presented mild partial epilepsy. The other three patients included one who experienced frequent non-convulsive status epilepticus and two who had early spasms. These three patients had also neurodevelopmental abnormalities and were diagnosed as developmental epileptic encephalopathy (DEE), but achieved seizure-free after antiepileptic-drug treatment without adrenocorticotropic-hormone\/steroids. The analyses of temporal expression (genetic dependent stages) indicated that\n                      <jats:italic>ZFHX3<\/jats:italic>\n                      orthologous were highly expressed in the embryonic stage and decreased dramatically after birth.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>ZFHX3<\/jats:italic>\n                      is a novel causative gene of childhood partial epilepsy and DEE. The patients of infantile spasms achieved seizure-free after treatment without adrenocorticotropic-hormone\/steroids implies a significance of genetic diagnosis in precise treatment. The genetic dependent stage provided an insight into the underlying mechanism of the evolutional course of illness.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jmg-2023-109725","type":"journal-article","created":{"date-parts":[[2024,6,2]],"date-time":"2024-06-02T06:38:36Z","timestamp":1717310316000},"page":"652-660","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["<i>ZFHX3<\/i>\n                    variants cause childhood partial epilepsy and infantile spasms with favourable 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