Topic: PRRT2

Patients with mutations in the PRRT2 gene (proline-rich transmembrane protein 2) are characterized by a large spectrum of neurological disorders, including mainly benign epilepsy and paroxysmal kinesigenic dyskinesia. PRRT2 is a neuronal protein implicated in the modulation of the voltage-gated sodium channel, in particular NaV 1.2 and 1.6. Indeed, a dysregulation of this gene could lead to hyperexcitability due to the loss of the Na+ channel modulation. To better understand the mechanism, we generated glutamatergic induced neurons (glutamatergic iNeurons) from PRRT2 induced pluripotent stem c

Mutations in TMEM151A, an almost unknown gene, have been recently found in Paroxysmal Kinesigenic Dyskinesia (PKD), an autosomal dominant movement disorder and in few cases of Benign Familial Infantile Epilepsy (BFIE). The major gene associated to PKD and BFIE is PRRT2. Interestingly, the drug treatment of choice for PKD caused by TMEM151A or PRRT2 mutations is Carbamazepine, a sodium channel blocker. Indeed, PRRT2 has been shown to control neuronal excitability by modulating voltage gated sodium channels. Both PRRT2 and TMEM151A are membrane associated proteins expressed in the nervous system