Abstract
Progressive Myoclonic Epilepsies (PMEs) are a rare and heterogeneous group of epileptic disorders often with progressive neurologic deterioration. The intensity of the clinical features varies depending on the underlying genetic etiology. This study aims to identify the genetic mutation associated with PME in a family belonging to the Iranian-Azeri-Turkish ethnic population. A 5-year-old boy and his 8-year-old sister, presenting with PME-related electroclinical features such as myoclonic seizures and progressive cognitive and motor decline, underwent comprehensive clinical evaluations, including pedigree analysis, laboratory tests, and EEG assessments, followed by Whole-Exome Sequencing (WES) to identify potential disease-causing mutations. We identified a novel homozygous mutation (c.14C > T) in the KCTD7 gene in both siblings, confirmed through Sanger sequencing. This mutation was not observed in a cohort of 430 healthy individuals from the same Iranian-Azeri-Turkish ethnic background, providing strong evidence for its pathogenic role. This finding advances our understanding of the genetic basis and phenotypic diversity of PMEs, but further research is needed to elucidate how KCTD7 mutations contribute to epilepsy and neurodegeneration.