P-EP012. Segregation of GABRA1 and ERBB4 mutations in a family with genetic generalized epilepsy

Abstract

Introduction . Genetic generalized epilepsy (GGE) accounts for 15-20% of the epilepsy cases. It is termed “genetic” as it has no known or suspected aetiology, other than possible hereditary predisposition. The objective of this study is to identify causative variants of GGE in a Chinese family with variable epilepsy phenotypes. Methods . Whole exome sequencing was first conducted on the proband. Candidate variants were validated, and the segregation study with other family members was performed using Sanger DNA sequencing. Results . The proband was a 30-year-old female with mixed syndromes of juvenile myoclonic epilepsy and temporal lobe epilepsy. Whole exome sequencing identified two mutations in the proband: c.448G>A in GABRA1 and c.1972A>T in ERBB4. Segregation analysis showed that the GABRA1 mutation was inherited from the father whereas the ERBB4 mutation was inherited from the mother. However, no history of epilepsy was observed in both the parents. The two mutations were also detected in her affected sister diagnosed with GGE without myoclonic jerks. Meanwhile, these mutations were absent in the unaffected brother. Interestingly, only the GABRA1 mutation was found in the daughter of the proband, who was diagnosed as focal epilepsy. Conclusion . Based on the genetic data and clinical evidence, we hypothesize that the GGE in this family may be largely caused by the inheritance of both susceptible GABRA1 and ERBB4 mutations. GABRA1 and ERBB4 have been shown to be interacting with each other in mouse model. Further studies are needed to support these findings.