Rationale:
Febrile seizure (FS) is associated with a febrile illness (temperature of 38°C or higher) not caused by central nervous system infection, without neurologic deficits in children aged 6-60 months. The segregation analysis implied a polygenic model in the families of proband(s) with single FS, while in families with repeated FS, inheritance was matched to autosomal dominance with reduced disease penetrance.
Method:
Targeted exome sequencing was conducted in combination with epilepsy/seizure related gene-filtering to identify the possible causative mutation in a Korean family with febrile and afebrile seizures.
Results:
The targeted exome sequencing identified a heterozygous c.2039A >G of the ADGRV1 gene causing a codon change of aspartic acid to glycine at the position 680 (rs547076322). This protein’s glycine residue is highly conserved, and its allele frequency is 0.00002827 in the population.
Conclusion:
A candidate mutation of the ADGRV1 (c.2039A>G, p.Asp680Gly) may lead to familial febrile seizure 4 with febrile and afebrile seizures. ADGRV1 variation may be an important contributor to the development of genetic epilepsies, particularly those with febrile and afebrile seizures. Further investigation of ADGRV1 mutations suggests that it will prove to be a significant susceptible gene for FS and/or afebrile seizure in early childhood.
Funding:
:none
FIGURES
Figure 1