Effects of PRRT2 mutation on brain gray matter networks in paroxysmal kinesigenic dyskinesia

Although proline-rich transmembrane protein 2 is the primary causative gene of paroxysmal kinesigenic dyskinesia, its effects on the brain structure of paroxysmal kinesigenic dyskinesia patients are not yet clear. Here, we explored the influence of proline-rich transmembrane protein 2 mutations on similarity-based gray matter morphological networks in individuals with paroxysmal kinesigenic dyskinesia. A total of 51 paroxysmal kinesigenic dyskinesia patients possessing proline-rich transmembrane protein 2 mutations, 55 paroxysmal kinesigenic dyskinesia patients possessing proline-rich transmembrane protein 2 non-mutation, and 80 healthy controls participated in the study. We analyzed the structural connectome characteristics across groups by graph theory approaches. Relative to paroxysmal kinesigenic dyskinesia patients possessing proline-rich transmembrane protein 2 non-mutation and healthy controls, paroxysmal kinesigenic dyskinesia patients possessing proline-rich transmembrane protein 2 mutations exhibited a notable increase in characteristic path length and a reduction in both global and local efficiency. Relative to healthy controls, both patient groups showed reduced nodal metrics in right postcentral gyrus, right angular, and bilateral thalamus; Relative to healthy controls and paroxysmal kinesigenic dyskinesia patients possessing proline-rich transmembrane protein 2 non-mutation, paroxysmal kinesigenic dyskinesia patients possessing proline-rich transmembrane protein 2 mutations showed almost all reduced nodal centralities and structural connections in cortico-basal ganglia-thalamo-cortical circuit including bilateral supplementary motor area, bilateral pallidum, and right caudate nucleus. Finally, we used support vector machine by gray matter network matrices to classify paroxysmal kinesigenic dyskinesia patients possessing proline-rich transmembrane protein 2 mutations and paroxysmal kinesigenic dyskinesia patients possessing proline-rich transmembrane protein 2 non-mutation, achieving an accuracy of 73%. These results show that proline-rich transmembrane protein 2 related gray matter network deficits may contribute to paroxysmal kinesigenic dyskinesia, offering new insights into its pathophysiological mechanisms.