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Successful control with carbamazepine of family with paroxysmal kinesigenic dyskinesia of PRRT2 mutation.

ABSTRACT: Paroxysmal kinesigenic dyskinesia (PKD), a rare paroxysmal movement disorder often misdiagnosed as epilepsy, is characterized by recurrent, brief dyskinesia attacks triggered by sudden voluntary movement. Pathophysiological mechanism of PKD remains not well understood. Ion channelopathy has been suggested, since the disease responds well to ion channel blockers. Mutations in proline-rich transmembrane protein 2 (PRRT2) were recently identified in patients with familial PKD. To extend these genetic reports, we studied a family with clinical manifestations of familial PKD responding well to low dose carbamazepine. Therapeutic dose ranged from 1.5 to 2.0 mg/ kg/day, below that in seizure control. One insertion mutation c.649_650insC (p.P217fsX7) was identified in three patients of the family. This study avers PRRT2's high sensitivity for PKD phenotype. Identification of genes underlying pathogenesis will enhance diagnosis and treatment. Function of PRRT2 and its role in PKD warrant further investigation.

SUBMITTER: Chou IC

PROVIDER: S-EPMC4265013 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Novel PRRT2 mutation in an African-American family with paroxysmal kinesigenic dyskinesia.

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Project description:BACKGROUND:Mutations in the PRRT2 gene have recently been identified in patients with familial paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) and patients with sporadic PKD/IC from several ethnic groups. To extend these recent genetic reports, we investigated the frequency and identities of PRRT2 mutations in a cohort of Taiwanese patients with PKD/IC. METHODOLOGY AND PRINCIPAL FINDINGS:We screened all 3 coding exons of PRRT2 for mutations in 28 Taiwanese patients with PKD/IC. Among them, 13 had familial PKD/IC and 15 were apparently sporadic cases. In total, 7 disparate mutations were identified in 13 patients, including 8 familial cases and 5 apparently sporadic cases. The mutations were not present in 500 healthy controls. Four mutations were novel. One patient had a missense mutation and all other patients carried PRRT2 mutations putatively resulting in a protein truncation. Haplotype analysis revealed that 5 of the 7 patients with the PRRT2 p.R217Pfs*8 mutation shared the same haplotype linked to the mutation. CONCLUSIONS AND SIGNIFICANCE:PRRT2 mutations account for 61.5% (8 out of 13) of familial PKD/IC and 33.3% (5 out of 15) of apparently sporadic PKD/IC in the Taiwanese cohort. Most patients with the PRRT2 p.R217Pfs*8 mutation in Taiwan likely descend from a single common ancestor. This study expands the spectrum of PKD/IC-associated PRRT2 mutations, highlights the pathogenic role of PRRT2 mutations in PKD/IC, and suggests genetic heterogeneity within idiopathic PKD.

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