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Cited by 345Epilepsy research and treatmentIon channel regulation and functionPharmacological Effects and Toxicity Studies

Mutations of sodium channel alpha subunit type 1 (SCN1A) in intractable childhood epilepsies with frequent generalized tonic-clonic seizures

Fujiwara, T.·2003·Brain
DOI 10.1093/brain/awg053
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Abstract

A group of infant onset epilepsies manifest very frequent generalized tonic-clonic seizures (GTC) intractable to medical therapy, which may or may not be accompanied by minor seizures such as myoclonic seizures, absences and partial seizures. They include severe myoclonic epilepsy in infancy (SMEI) and intractable childhood epilepsy with GTC (ICEGTC). They are commonly associated with fever-sensitivity, family history of seizure disorders and developmental decline after seizure onset. Mutations of the neuronal voltage-gated sodium channel alpha subunit type 1 gene (SCN1A) were recently reported in SMEI patients. To clarify the genotypic differences in this group of epilepsies, we searched for SCN1A abnormalities in 25 patients with SMEI and 10 with ICEGTC, together with the family members of 15 patients. Frameshift mutations in SCN1A were observed in four patients, nonsense mutations in five patients, missense mutations in 21 patients, other mutations in two patients and no mutation in five patients. SMEI patients showed nonsense mutations, frameshifts, or missense mutations, while ICEGTC patients showed only missense mutations. Study of both parents of 11 patients revealed that the mutations in these patients were de novo. However, two mothers had the same missense mutations as their ICEGTC children, and they had generalized epilepsy with febrile seizures plus. Here we suggest that SMEI and ICEGTC represent a continuum with minor phenotypic and genotypic differences.

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Crossref · 10.1093/brain/awg053

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  • Genomic sequencing data indicate that a number of mutations in the Scn1a gene contribute to a spectrum of different epileptic disorders affecting children, including de novo as well as missense, frame-shift, and nonsense mutations.

    “Genomic sequencing data indicate that a number of mutations in the Scn1a gene contribute to a spectrum of different epileptic disorders affecting children, including de novo (Claes et al., 2001; Fujiwara et al., 2003) as well as missense, frame-shift, and nonsense mutations (Fujiwara et al., 2003).”

    From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Fujiwara et al., 2003

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Authors
Fujiwara, T.
Affiliations
National Epilepsy Center (JP)
Corresponding author
Fujiwara, T.
Venue
Brain
Publisher
Oxford University Press (OUP)
Published
2003-03-01
Volume
126
Issue
3
Pages
531-546
ISSN
  • 0006-8950 (ISSN-L)
  • 1460-2156
DOI
10.1093/brain/awg053
OpenAlex
W2161749769
Cited by
345
References
32
Citations by year
2026: 2 · 2025: 4 · 2024: 5 · 2023: 8 · 2022: 7 · 2021: 13 · 2020: 36 · 2019: 6 · 2018: 5 · 2017: 10 · 2016: 11 · 2015: 14 · 2014: 19 · 2013: 19 · 2012: 12
FWCI
13.67
Type
journal article
Language
en
Open access
closed
Locations
  • Brain (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
Keywords
SCN1A, Dravet syndrome, generalized tonic-clonic seizures, missense mutations, frameshift mutation, nonsense mutation, de novo mutations, generalized epilepsy with febrile seizures plus, genotype-phenotype correlation, infantile epilepsy
MeSH terms
Adolescent, Adult, Body Temperature, Child, Child, Preschool, Seizures, Febrile, DNA Mutational Analysis, Epilepsy, Tonic-Clonic, Epilepsies, Myoclonic, Female, Heterozygote, Humans, Male, Nerve Tissue Proteins, Sodium Channels, Frameshift Mutation, Mutation, Missense, NAV1.1 Voltage-Gated Sodium Channel

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