Clinical Phenotype and Omics Study of KCNQ2-related Epilepsy

Clinical Phenotype and Omics Study of KCNQ2-related Epilepsy

The aims of study on KCNQ2-related epilepsy: (1) establish phenotype database and sample database of KCNQ2-related epilepsy; (2) to establish genotype-phenotype association of KCNQ2-related epilepsy; (3) to study the brain network of KCNQ2-related epilepsy based on multi-modal brain image and EEG data; (4) to find prognostic biomarkers of KCNQ2-related epilepsy based on omics study.

1. Participant recruitment: participants are recruited from Chinese KCNQ2-related epilepsy patients group (http://www.kcnq2.cn/). According to the clinical phenotype, the participants will be divided into benign familial neonatal seizures (BFNS) group and Developmental and epileptic encephalopathy (DEE) group.
2. Genotype-phenotype association: electrophysiological detection of KCNQ2 mutation will be performed using patch clamp technique in an in vitro cell model. The association between phenotype (such as epileptic phenotype, developmental assessment and drug response) and genotype will be analyzed.
3. Brain network analysis: participants who provide informed consent will be scaned by brain magnetic resonance imaging (MRI) or positron emission tomography-computed tomography (PET-CT) and monitored by the electroencephalogram (EEG). The Brain Network of KCNQ2-related epilepsy will be analyzed based on multi-modal brain image and EEG between BFNS and DEE group.
4. Omics Study: after informed consent, blood, urine and feces samples of participants will be taken. The samples were tested for omics study including proteomics, metabolomics, transcriptomics, to analysis the difference of BFNS and DEE group.

Inclusion Criteria:

• KCNQ2 mutation was confirmed by WES, Panel and other gene tests;
• Clinically diagnosed as epilepsy;
• KCNQ2 mutation was identified as pathogenic or possibly pathogenic according to ACMG pathogenicity rating standard;
• Age and gender are not limited;
• No abnormal birth history;
• Informed consent and willingness to follow up

Exclusion Criteria:

• Patients with KCNQ2 mutation without epilepsy;
• Other possible pathogenic gene mutations except KCNQ2;
• Large cross-gene deletions or duplications including KCNQ2;
• Unable to participate in the study follow-up