Features Differ Between Paroxysmal Kinesigenic Dyskinesia Patients with PRRT2 and TMEM151A Variants

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Mutations in proline-rich transmembrane protein 2 (PRRT2) are the primary genetic cause of paroxysmal kinesigenic dyskinesia (PKD).
• Recent findings identified mutations in transmembrane protein 151A (TMEM151A) as another cause of PKD.
• This study aimed to compare the clinical phenotypes of PKD patients with PRRT2 variants, TMEM151A variants, and neither.

Purpose of the Study:

• To conduct a phenotypic comparison between patients with paroxysmal kinesigenic dyskinesia (PKD) associated with PRRT2 variants and those with TMEM151A variants.
• To identify distinct clinical characteristics that differentiate PKD caused by PRRT2 mutations from PKD caused by TMEM151A mutations.

Main Methods:

• Sanger sequencing was employed to identify variants in the PRRT2 and TMEM151A genes.
• Phenotypic characteristics of 131 PKD probands were analyzed and compared based on their genetic findings.

Main Results:

• Five novel TMEM151A variants were identified in the PKD cohort, with one occurring de novo.
• PRRT2 and TMEM151A variants accounted for 34.7% and 6.9% of PKD probands, respectively.
• Patients with TMEM151A variants exhibited shorter durations of dystonia, lacked a history of benign infantile epilepsy, and showed residual attacks/aura when treated with carbamazepine/oxcarbazepine, distinguishing them from PRRT2 variant carriers.

Conclusions:

• Patients with TMEM151A variants present with distinct clinical features compared to those with PRRT2 variants.
• These findings highlight the genetic heterogeneity of PKD and the importance of considering TMEM151A in the genetic diagnosis.
• Understanding these phenotypic differences can aid in more accurate diagnosis and potentially tailored treatment strategies for PKD.