Study on gene mutation in benign familial neonatal epilepsy

Objective To investigate the gene mutations in benign familial neonatal epilepsy(BFNE) in China. Methods Data of all BFNE probands and their family members were collected from Peking University First Hospital from January 2012 to December 2013.Clinical phenotypes of affected members were analyzed.Genomic DNA was extracted from peripheral blood samples with standard protocol.Mutations in candidate genes mutations were further screened by next-generation sequencing. Results A total of 4 families were collected, from which there were 10 affected members, 6 males and 4 females.The age of epilepsy onset was from 1 day to 4 days after birth.The age of last seizure was from 3 days to 3 years and 10 months old.The age of last follow-up was from 4 years and 3 months old to 37 years old.All affected members had normal development.Genetic testing identified KCNQ2 mutations in 3 families (75%, 3/4 cases). Two families had missense KCNQ2 mutations (c.1048A>C/p.N350H and c. 242T>C/p.L81P). One family had nonsense KCNQ2 mutation(c.2506G>T/p.E836X). The other 3 KCNQ2 mutations were novel.The remaining BFNE family was not detected with any pathogenic mutation.The age of inital seizure onset of the proband was 1 day after birth.The seizures got controlled at 3 months old.However, this proband had another 2 afebrile seizures during sleep at 3 years and 10 months old.Electroenlephalography monitoring showed focal central temporal spikes.It is speculated that the seizures had evolved into benign epilepsy of childhood with central temporal spikes. Conclusions Mutations in KCNQ2 are major genetic causes in Chinese families with BFNE.KCNQ2 mutation c. 1048A>C/p.N350H, c.242T>C/p.L81P, and c. 2506G>T/p.E836X are novel mutations.Identification of underlying gene mutation can be helpful for clinical diagnosis and judgment of the prognosis. Key words: Benign familial neonatal epilepsy; KCNQ2 gene; Gene mutation