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

Elisabeth Herini (Department of Child Health, Gadjah Mada University Medical School/Dr. Sardjito Hospital, Yogyakarta, Central Java)
Yudha Patria (Department of Child Health, Gadjah Mada University Medical School/Dr. Sardjito Hospital, Yogyakarta, Central Java)
Gunadi Gunadi (Department of Genetic Epidemiology, Kobe University Graduate School of Medicine, Kobe)
Surini Yusoff (Department of Genetic Epidemiology, Kobe University Graduate School of Medicine, Kobe)
Indra SAri Kusuma Harahap (Department of Genetic Epidemiology, Kobe University Graduate School of Medicine, Kobe)
Sunartini Sunartini (Department of Child Health, Gadjah Mada University Medical School/Dr. Sardjito Hospital, Yogyakarta, Central Java)
Sutaryo Sutaryo (Department of Child Health, Gadjah Mada University Medical School/Dr. Sardjito Hospital, Yogyakarta, Central Java)
Satoshi Takada (Department of Community Health Science, Kobe University Graduate School of Medicine, Kobe)
Hisahide Nishio (Department of Genetic Epidemiology, Kobe University Graduate School of Medicine, Kobe)

Paediatrica Indonesiana
Vol 50 No 3 (2010): May 2010

Background Mutations in the a-subunit of the first neuronalsodium channel gene SCNIA have been demonstrated forgeneralized epilepsy \\lith febrile seizures plus (GEFS+), severemyoclonic epilepsy in infancy (SMEI), and borderline SMEI(SMEB). SCNIA mutations are also described in patients 'Withpsychiatric disorders such as autism.Objective To identify the mutations of SCNIA gene in patientswith GEFS+ spectrum which may be related to autism.Methods We examined four patients v.ith autism and GEFS+spectrum who were admitted to the Department of Child Health,Sardjito Hospital, Yogyakarta, Indonesia. Diagnosis of autism wasbased on DSM􀁟IV;ICD X criteria. Mutations in SCNIA wereidentified by PCRamplification and denaturing high􀁟performanceliquid chromatography analysis, Mth 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, SMEBin one patient and SMEI in two patients. Sequencing analysisrevealed a G􀁟to􀁟A heterozygous transition which was detectedat nucleotide c.4834G>A (p.V1612I ) in exon 25. Other singlenucleotid polymorphisms (SNPs) were c.383 +66T>C in intron 2,c.603-91G>A and c.603-1060> T in intron 4, c.965-21C> T inintron 6, c.1028+21T>Cin intron 7, c.2173G>A in exon 12 andc. 2177-38C>A, c.2177-12delT, c.2176+44C> T in intron 12.Conclusion In this study, we reported the first cases Mth mutationin SCNIA gene in GEFS+ spectrum related to autistic patientsin Indonesian population, which showed a missense mutationp.V16121. [Paediatr lndones. 2010;50:125-32].