Sodium channels of SCN1A gene mutations in generalized epilepsy with febrile seizure plus (GEFS+) spectrum related to autism

Background Mutations in the a subunit of the first neuronal sodium generalized epilepsy with febrile seizures plus (GLTS+), severe myoclonic epilepsy in infancy (SMEI), and borderline SMEI (SMEB). SCNIA mutations are also described in patients with psychiatric disorders such as autism. Objective To identify the mutations of SCNIA gene in patients with OEFS + spectrum which may be related to autism. Methods We examined four patients with autism and GEFS+ spectrum who were admitted to the Department of Child Health, Sardjito Hospital, Yogyakarta, Indonesia. Diagnosis of autism was based on DSM-IV/ICD X criteria. Mutations in SCNIA were identified 13y PCR amplification and denaturing high-performance liquid chromatography analysis, with subsequent sequencing. Results There were four patients, all boys, aged 1.8 year to 7 years. The phenotypes of epilepsy were GEFS+ in one patient, SMEB in one patient and SMEI in two patients. Sequencing analysis revealed a G-to-A heterozygous transition which was detected at nucleotide c.48340 > A (p.V1612I) in exon 25. Other single nucleotid polymorphisms (SNP) were c.383+66T>C in intron 2, c.603-910>A and c.603-1060>T in intron 4, c.965-21C>T in intron 6, c.1028 + 21T>C in intron 7, c.21730>A in exon 12 and c. 2177-38C>A, c.2177-12delT, c.2176+44C>T in intron 12. Conclusion In this study, we reported the first cases with mutation in SCNIA gene in GEFS+ spectrum related to autistic patients in Indonesian population, which showed a missense mutation p.V1612I.