PRRT2 mutations are the major cause of benign familial infantile seizures

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Mutations in the proline-rich transmembrane protein 2 (PRRT2) gene are associated with paroxysmal kinesigenic dyskinesia (PKD) and infantile convulsions with choreoathetosis.
• Recent studies suggest PRRT2 mutations may also cause benign familial infantile seizures (BFIS) in isolation.

Purpose of the Study:

• To investigate the role of PRRT2 mutations in families presenting solely with benign familial infantile seizures (BFIS).
• To identify the frequency of known and novel PRRT2 mutations in a cohort of BFIS patients from diverse ethnic backgrounds.

Main Methods:

• Genetic analysis of the PRRT2 gene in 49 families and 3 sporadic cases with BFIS.
• Screening for known mutations, specifically c.649dupC, and identification of novel mutations.
• Analysis of mutation prevalence across different ethnic groups (Italian, German, Turkish, Japanese).

Main Results:

• The c.649dupC mutation in PRRT2 was identified in 77% of index cases with BFIS.
• Three novel PRRT2 mutations were discovered in three additional families.
• Approximately 17% of BFIS cases, including a late-onset family with febrile seizures, did not show PRRT2 mutations.

Conclusions:

• PRRT2 is confirmed as the major causative gene for benign familial infantile seizures (BFIS) presenting alone.
• The findings highlight the significant contribution of PRRT2 mutations to BFIS etiology.
• Further research may be needed to identify genetic factors in PRRT2-negative BFIS cases.