Epilepsy with auditory features: A heterogeneous clinico-molecular disease

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Epilepsy with auditory features (EAF) is a heterogeneous neurological disorder with an unknown molecular basis in many families.
• Previous research has excluded mutations in the LGI1 gene in the studied cohort.

Purpose of the Study:

• To identify novel genes associated with epilepsy with auditory features (EAF) in families with complex genetic backgrounds.
• To expand the understanding of the genetic underpinnings of EAF.

Main Methods:

• Whole-exome sequencing (WES) was performed on 20 individuals from 15 families with EAF.
• Electroclinical phenotyping was conducted on probands and available affected relatives.
• Analysis included single nucleotide variants, small insertions/deletions, and copy number variants.

Main Results:

• Likely pathogenic variants were identified in CNTNAP2 (intragenic deletion), DEPDC5 (2 truncating mutations), and SCN1A (1 missense change).
• These genes were not previously associated with EAF.
• The identified variants expand the known genetic spectrum for EAF.

Conclusions:

• Epilepsy with auditory features (EAF) is genetically diverse.
• Mutations in CNTNAP2, DEPDC5, and SCN1A are implicated in EAF, broadening the phenotypic spectrum of these genes.
• The findings highlight the role of the CNTNAP2-encoded CASPR2 protein in the voltage-gated potassium channel complex, suggesting biological convergence in EAF pathogenesis.