[Mutation analysis of the SCN1A gene in severe myoclonic epilepsy of infancy].
OBJECTIVE
To investigate the mutations of the sodium channel alpha 1 subunit gene SCN1A in severe myoclonic epilepsy of infancy (SMEI) patients and analyze its inheritance.


METHODS
Twenty-three patients consistent with the diagnosis of SMEI were selected for SCN1A mutation analysis. Genomic DNA was extracted from peripheral blood lymphocytes of these patients and their parents. All the twenty-six exons of the SCN1A gene were amplified by PCR and sequenced.


RESULTS
In the 23 SMEI patients, 17 mutations were identified in 17 unrelated SMEI patients. The SCN1A mutation rate was 73.9% (17/23). The mutations included 8 missense mutations (F90S, I91T, A239T, W952G, T1210K, V1335M, V1390M and G1433E), 3 nonsense mutations (R612X, W768X and W1408X), 3 deletion mutations (A395fsX400, L556fsX557 and V1778fsX1800), 1 insertion mutation (Y1241fsX1270), 1 splice-site mutation (IVS10+3 A to G) and 1 synonymous mutation (K1492K), of which 47.1% (8/17) were truncation mutations. Thirteen mutations (F90S, I91T, T1210K, V1335M, G1433E, R612X, W768X, A395fsX400, L556fsX557, V1778fsX1800, Y1241fsX1270, IVS10+3A to G and K1492K) have not been reported previously. Except for F90S, L556fsX557 and V1778fsX1800, the other 14 mutations were de novo.


CONCLUSIONS
SCN1A is a major pathogenic gene for SMEI. About a half of the SCN1A mutations in SMEI cause truncation. There were no hotspots of SCN1A mutations in SMEI patients, and most mutations were de novo.
Sun
Huihui
H
Department of Pediatrics, the First Hospital of Peking University, Beijing, 100034 P. R. China. zhangyhdr@126.com.
Zhang
Yuehua
Y
Liu
Xiaoyan
X
Ma
Xiuwei
X
Wu
Husheng
H
Xu
Keming
K
Qin
Jiong
J
Qi
Yu
Y
Wu
Xiru
X
D000293:Adolescent; D017668:Age of Onset; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D004831:Epilepsies, Myoclonic / Q000175:diagnosis / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D016415:Sequence Alignment; D017384:Sequence Deletion; D015222:Sodium Channels / Q000235:genetics*
D018389:Codon, Nonsense; D009419:Nerve Tissue Proteins; D015222:Sodium Channels