[P3-68] Novel KCNQ4 gene mutations contribute to susceptibility of genetic febrile seizures
[Objective]: To identify genes potentially accounting for pathogenesis of genetic febrile seizures. [Methods]: 31 febrile seizures families and 200 healthy patients were included in this study. A high throughput gene capture ap¬proach was used to identify candidate genes which were then validated using Sanger sequencing. Pedigree analysis was applied to evaluate phenotype and genotype. Sequencing PCR products was used to screen gene mutations in the control group. [Results]: We found three KCNQ4 gene missense mutations c.1609C>T (P537S), c.1207G>A (A403T), and c.1177G>T (G393C) in exons 9, 10, and 13, respectively. Each patient only had one of these mutations among three of all 31 febrile seizures families. KCNQ4 gene mutations were not found in the other 28 febrile sei¬zures families and the healthy control group. We also found a missense SCN5A gene mutation c.2893C>T (R965C) in proband 1 family but not the other two febrile seizures families. Pedigree analysis indicated that some mutation-carriers in these members were not febrile seizures. However, the proband 1 and his elder brother carried both the KCNQ4 and SCN5A gene mutations, and probands 2 and 3 carried KCNQ4 gene mutation. [Conclusion]: Novel KCNQ4 gene mutations and SCN5A gene mutation were not single causal factors for febrile seizures. They most likely inter¬acted with other gene mutations to promote a susceptibility to febrile seizures. Our findings add to the literature that KCNQ4 gene mutations are previously found to be only associated with hearing loss. Our finding provides a new clue to investigate the genetic etiology of febrile seizures.