Genetic variants in incident SUDEP cases from a community-based prospective cohort with epilepsy
Yan Ge1, Ding Ding2, Guoxing Zhu1
1Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
Objective:
Sudden unexpected death in epilepsy (SUDEP) is a leading cause of epilepsy-related mortality in young adults. It has been suggested that SUDEP may kill over 20 000 people with epilepsy in China yearly. The aetiology of SUDEP is unclear. Little is known about candidate genes for SUDEP in people of Chinese origin as most studies have ascertained this in Caucasians. No candidate genes for SUDEP in Chinese people have been identified.
Methods:
We performed whole exome sequencing (WES) in DNA samples collected from five incident cases of SUDEP identified in a large epilepsy cohort in rural China. We filtered rare variants identified from these cases as well as screened for SUDEP, epilepsy, heart disease or respiratory disease-related genes from previous published reports and compared them with publicly available data, living epilepsy controls and ethnicity-match non-epilepsy controls, to identify potential candidate genes for SUDEP.
Results:
After the filtering process, the five cases carried 168 qualified mutations in 167 genes. Among these genetic anomalies, we identified rare variants in SCN5A (1/5:20% in our cases), KIF6 (1/5:20% in our cases) and TBX18 (1/5:20% in our cases) which were absent in 330 living epilepsy control alleles from the same original cohort and 320 ethnicity-match non-epilepsy control alleles.
Conclusions:
These three genes were previously related to heart disease, providing support to the hypothesis that underlying heart disorder may be a driver of SUDEP risk.
More Related Videos
Related Concept Videos
Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
Epilepsy and Seizures: Overview
Various factors can trigger epilepsy, including genetic factors, brain damage, metabolic causes, and unknown etiology. Diagnosis of epilepsy involves electroencephalography (EEG), which...
Seizures: Classification
Seizures are typically classified into two main categories: focal and generalized seizures.
Focal Seizures
Focal seizures originate from specific regions of the brain. These seizures are further sub-classified into two types:
Comparing Copy Number Variations and SNPs
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Prevalence and Incidence
Prevalence indicates the proportion of individuals in a population who have a specific disease or health...
Single Nucleotide Polymorphisms-SNPs


