Novel KCNC2 variant associated with developmental and epileptic encephalopathy

Area of Science:

• Neurogenetics
• Molecular Biology
• Epilepsy Research

Background:

• The KCNC2 gene encodes the Kv3.2 potassium channel subunit, essential for neuronal excitability.
• Kv3.2 channels are critical for the fast-spiking activity of cortical GABAergic interneurons.
• KCNC2 gene variations have been recently implicated in epileptic encephalopathy.

Purpose of the Study:

• To report a novel KCNC2 gene variant in a Chinese patient diagnosed with developmental and epileptic encephalopathy (DEE).
• To investigate the genetic basis of DEE in a Chinese family using whole-exome sequencing (WES).
• To contribute to the understanding of KCNC2-associated epilepsy and the utility of WES reanalysis.

Main Methods:

• Whole-exome sequencing (WES) was performed on a Chinese patient with DEE and motor delay.
• A novel heterozygous variant (NM_139137.4:c.1163T>C, p.Phe388Ser) in the KCNC2 gene was identified.
• Sanger sequencing confirmed the de novo status of the mutation, and WES data reanalysis identified the variant in a family cohort.

Main Results:

• A novel de novo heterozygous variant, KCNC2:c.1163T>C (p.Phe388Ser), was identified in a Chinese patient with DEE.
• This variant is classified as likely pathogenic, associated with the patient's severe neurological phenotype.
• Reanalysis of WES data confirmed the presence of this KCNC2 variant in the affected family.

Conclusions:

• The study identifies a new KCNC2 pathogenic variant contributing to DEE in a Chinese population.
• This finding expands the genotypic spectrum of KCNC2-related epilepsy.
• The results highlight the importance of WES technology and data reanalysis for diagnosing rare genetic epilepsy disorders.