Premium
Novel SCN1A mutations in Indonesian patients with severe myoclonic epilepsy in infancy
Author(s) -
Herini Elisabeth Siti,
Van Kempen Marjan J.A.,
Yusoff Surini,
Patria Suryono Yudha,
Matsuo Masafumi,
Lindhout Dick,
Nishio Hisahide
Publication year - 2010
Publication title -
pediatrics international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.49
H-Index - 63
eISSN - 1442-200X
pISSN - 1328-8067
DOI - 10.1111/j.1442-200x.2009.02916.x
Subject(s) - transversion , medicine , valine , myoclonic epilepsy , exon , genetics , mutation , compound heterozygosity , denaturing high performance liquid chromatography , microbiology and biotechnology , amino acid , gene , epilepsy , biology , psychiatry
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 α1‐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. Conclusion: 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.