The objective of this study was to investigate potential causative genes and clinical characteristics in proline-rich transmembrane protein 2-negative patients with paroxysmal kinesigenic dyskinesia.
Next-generation sequencing was used to determine the chromosomal deletion sites in patients with PRRT2 copy number variants, and to exclude mutations in other known causative genes for paroxysmal kinesigenic dyskinesia.
The identification of heterozygous mutations in the PRRT2 gene in paroxysmal kinesigenic dyskinesia as well as in benign familial infantile seizures linked episodic movement disorders with epilepsy.
Benign familial infantile epilepsy (41.7%; n = 602), paroxysmal kinesigenic dyskinesia (38.7%; n = 560) and infantile convulsions and choreoathetosis (14.3%; n = 206) constitute the vast majority of PRRT2-associated diseases, leaving 76 patients (5.3%) with a different primary diagnosis.
Mutations in Proline-rich Transmembrane Protein 2 (PRRT2) have been primarily associated with individuals presenting with infantile epilepsy, including benign familial infantile epilepsy, benign infantile epilepsy, and benign myoclonus of early infancy, and/or with dyskinetic paroxysms such as paroxysmal kinesigenic dyskinesia, paroxysmal non-kinesigenic dyskinesia, and exercise-induced dyskinesia.
To examine functional and structural connectivity of thalamocortical networks in paroxysmal kinesigenic dyskinesia and to further investigate the effect of mutation of the proline-rich transmembrane protein 2 on thalamocortical networks.
A PRRT2 variant in a Chinese family with paroxysmal kinesigenic dyskinesia and benign familial infantile seizures results in loss of interaction with STX1B.
PRRT2 mutations have recently been shown to cause various childhood-onset episodic syndromes including paroxysmal kinesigenic dyskinesia, infantile convulsions with choreoathetosis syndrome, and benign familial infantile epilepsy.
In an elegant publication in Cell Research, Tan and colleagues showed that ablation of PRRT2 in cerebellar granule cells is sufficient to induce paroxysmal kinesigenic dyskinesia.
We describe a family with paroxysmal kinesigenic dyskinesia associated with PRRT2 gene mutation, mild intrafamilial clinical heterogeneity, and benign course.[Published with video sequences].
We hypothesize a pathogenic role of PRRT2 mutation in inducing benign myoclonus of early infancy, similarly to that at the origin of other PRRT2-related paroxysmal movement disorders, such as paroxysmal kinesigenic dyskinesia.