biostudies-literatureHe MFScientific Research Project of Guangzhou Education BureauNational Natural Science Foundation of ChinaMulticenter Clinical Research Fund Project of the Second Affiliated Hospital of Guangzhou Medical UniversityScience and Technology Project of Guangzhou652-660https://www.ebi.ac.uk/biostudies/studies/S-EPMC11228202biostudies-literatureUnknown61(7)<h4>Background</h4>The <i>ZFHX3</i> gene plays vital roles in embryonic development, cell proliferation, neuronal differentiation and neuronal death. This study aims to explore the relationship between <i>ZFHX3</i> variants and epilepsy.<h4>Methods</h4>Whole-exome sequencing was performed in a cohort of 378 patients with partial (focal) epilepsy. A <i>Drosophila Zfh2</i> knockdown model was used to validate the association between <i>ZFHX3</i> and epilepsy.<h4>Results</h4>Compound heterozygous <i>ZFHX3</i> variants were identified in eight unrelated cases. The burden of <i>ZFHX3</i> variants was significantly higher in the case cohort, shown by multiple/specific statistical analyses. In <i>Zfh2</i> knockdown flies, the incidence and duration of seizure-like behaviour were significantly greJournal of medical genetics<i>ZFHX3</i> variants cause childhood partial epilepsy and infantile spasms with favourable outcomes.PMC11228202822715058187090381971216202235395202201020106010G2710992021-LCYJ-DZX-022020-LCYJ-DZX-03Zou DFZhou PWang PYLiu LHHe NYi YHWang JLiu XRLi BMGuo JJMa HYHe MFHe SLQiao JDLuo SZhai QXLiao WPfalse<i>ZFHX3</i> variants cause childhood partial epilepsy and infantile spasms with favourable outcomes.<h4>Background</h4>The <i>ZFHX3</i> gene plays vital roles in embryonic development, cell proliferation, neuronal differentiation and neuronal death. This study aims to explore the relationship between <i>ZFHX3</i> variants and epilepsy.<h4>Methods</h4>Whole-exome sequencing was performed in a cohort of 378 patients with partial (focal) epilepsy. A <i>Drosophila Zfh2</i> knockdown model was used to validate the association between <i>ZFHX3</i> and epilepsy.<h4>Results</h4>Compound heterozygous <i>ZFHX3</i> variants were identified in eight unrelated cases. The burden of <i>ZFHX3</i> variants was significantly higher in the case cohort, shown by multiple/specific statistical analyses. In <i>Zfh2</i> knockdown flies, the incidence and duration of seizure-like behaviour were significantly gre2024-01-01T00:00:00Z2024 Jun2026-06-07T07:48:18.111Z2026-06-07T03:11:52.325ZS-EPMC112282023850870510.1136/jmg-2023-109725