title: Novel SCN1A mutations in Indonesian patients with severe myoclonic epilepsy in infancy.
abstract: BACKGROUND
  Severe myoclonic epilepsy in infancy (SMEI) and borderline SMEI (SMEB) are caused by a mutation in SCN1A, which encodes a voltage-gated sodium channel alpha1-subunit protein. Although many mutations in SCN1A have been associated with clinical features of SMEI or SMEB from different ethnic groups, there have been no such reports from the South-East Asian populations so far.
  
  
  METHODS
  Patients 1 and 2 were Indonesian children diagnosed as having SMEI and SMEB based on their clinical features. SCN1A was screened for mutations using a combination of polymerase chain reaction and denaturing high-performance liquid chromatography. Nucleotide substitutions were confirmed on direct sequencing.
  
  
  RESULTS
  In patient 1, a G-to-A heterozygous transition was detected at nucleotide 4834 (c.4834G>A) in exon 25, leading to substitution of valine with isoleucine at amino acid position 1612 (p.V1612I) in the SCN1A protein. In patient 2 a T-to-G heterozygous transversion was identified at nucleotide 5266 (c.5266T>G) in exon 26, leading to substitution of cysteine with glycine at amino acid 1756 (p.C1756G) in the SCN1A protein. Both amino acid substitutions might disrupt these highly conserved regions in species from drosophila to human, leading to dysfunction of the protein. p.V1612I and p.C1756G were determined as disease-causing mutations due to their absence in the control population.
  
  
  CONCLUSIONS
  The first cases of SMEI and SMEB are reported in South-East Asian populations. Two novel SCN1A mutations are also identified in these patients, p.V1612I and p.C1756G, which may lead to neuronal excitability or convulsions.
authors: Department of Genetic Epidemiology, Kobe University Graduate School of Medicine, Kobe, Japan. herini_es@yahoo.com
authors: Elisabeth Siti
authors: ES
authors: Herini
authors: Gunadi
authors: Marjan J A
authors: MJ
authors: van Kempen
authors: Surini
authors: S
authors: Yusoff
authors: Sutaryo
authors: Sunartini
authors: Suryono Yudha
authors: SY
authors: Patria
authors: Masafumi
authors: M
authors: Matsuo
authors: Dick
authors: D
authors: Lindhout
authors: Hisahide
authors: H
authors: Nishio
mesh_terms: D002648:Child; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D006801:Humans; D007214:Indonesia; D007223:Infant; D008297:Male; D009154:Mutation; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D012720:Severity of Illness Index; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels