Functional Study of NIPA2 Mutations Identified from the Patients with Childhood Absence Epilepsy

摘要: Recently many genetic mutations that are associated with epilepsy have been identified. The protein NIPA2 (non-imprinted in Prader-Willi/Angelman syndrome region 2) is a highly selective magnesium transporter encoded by the gene which we found three (p.I178F, p.N244S and p.N334_E335insD) within population of patients childhood absence (CAE). In this study, immunofluorescence labeling, inductively coupled plasma-optical emission spectroscopy (ICP-OES), MTT metabolic rate detection computational modeling were utilized to elucidate how these result CAE. We cultured neurons (wild-type) proteins localized cell periphery, whereas mutant not effectively trafficked membrane. Furthermore, decrease intracellular concentration transfected NIPA2, but no effect on survival neurons. To understand low resulted hyperexcitability, built analyzed model simulate effects mutations. suggested lower enhanced synaptic N-methyl-D-aspartate receptor (NMDAR) currents. This study primarily reveals may play role pathogenesis