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

Elisabeth Herini; Yudha Patria; Gunadi Gunadi; Surini Yusoff; Indra SAri Kusuma Harahap; Sunartini Sunartini; Sutaryo Sutaryo; Satoshi Takada; Hisahide Nishio

doi:10.14238/pi50.3.2010.125-32

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

DOI: https://doi.org/10.14238/pi50.3.2010.125-32

Keywords: mutation, SCNIA, generalized epilepsy with febrile seizures plus, severe myoclonic epilepsy in infancy, autistic spectrum disorder

Abstract

Background Mutations in the a-subunit of the first neuronal
sodium channel gene SCNIA have been demonstrated for
generalized epilepsy \\lith febrile seizures plus (GEFS+), 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 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 was
based on DSMô€ŸIV;ICD X criteria. Mutations in SCNIA were
identified by PCRamplification and denaturing highô€Ÿperformance
liquid 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, SMEB
in one patient and SMEI in two patients. Sequencing analysis
revealed a Gô€Ÿtoô€ŸA heterozygous transition which was detected
at nucleotide c.4834G>A (p.V1612I ) in exon 25. Other single
nucleotid 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 in
intron 6, c.1028+21T>Cin intron 7, c.2173G>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 Mth mutation
in SCNIA gene in GEFS+ spectrum related to autistic patients
in Indonesian population, which showed a missense mutation
p.V16121. [Paediatr lndones. 2010;50:125-32].

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