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Microdeletions involving the SCN1A gene may be common in SCN1A-mutation-negative SMEI patients
- Source :
- Human mutation
- Publication Year :
- 2006
-
Abstract
- Severe myoclonic epilepsy of infancy (SMEI) or Dravet syndrome is a rare epilepsy syndrome. In 30 to 70% of SMEI patients, truncating and missense mutations in the neuronal voltage-gated sodium-channel α-subunit gene (SCN1A) have been identified. The majority of patients have truncating mutations that are predicted to be loss-of-function alleles. Because mutation detection studies use PCR-based sequencing or conformation sensitive gel electrophoresis (CSGE), microdeletions, which are also predicted to be loss-of-function alleles, can easily escape detection. We selected 11 SMEI patients with or without additional features who had no SCN1A mutation detectable with sequencing analysis. In addition, none of the patients was heterozygous for any of the SNPs in SCN1A, indicating that they were either homozygous for all SNPs or hemizygous due to a microdeletion of the gene. We subsequently analyzed these patients for the presence of microdeletions in SCN1A using a quantitative PCR method named multiplex amplicon quantification (MAQ), and observed three patients missing one copy of the SCN1A gene. All three microdeletions were confirmed by fluorescence in situ hybridization (FISH). These findings demonstrate that a substantial percentage of SCN1A-mutation-negative SMEI patients with or without additional features carry a chromosomal microdeletion comprising the SCN1A gene and that haploinsufficiency of the SCN1A gene is a cause of SMEI. Hum Mutat 27(9), 914–920, 2006. © 2006 Wiley-Liss, Inc.
- Subjects :
- Male
DNA Mutational Analysis
Mutation, Missense
Single-nucleotide polymorphism
Epilepsies, Myoclonic
Nerve Tissue Proteins
Biology
Polymerase Chain Reaction
Polymorphism, Single Nucleotide
Sodium Channels
Dravet syndrome
Genetics
medicine
Missense mutation
Humans
Genetic Testing
Child
Genetics (clinical)
In Situ Hybridization, Fluorescence
medicine.diagnostic_test
Haplotype
Chromosome Mapping
Infant
Amplicon
medicine.disease
Molecular biology
epilepsy
children
SMEI
SCN1A
NAV1.1 Voltage-Gated Sodium Channel
Haplotypes
Codon, Nonsense
Myoclonic epilepsy
Female
Haploinsufficiency
Gene Deletion
Fluorescence in situ hybridization
Subjects
Details
- ISSN :
- 10981004 and 10597794
- Volume :
- 27
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Human mutation
- Accession number :
- edsair.doi.dedup.....00b618b8406f0d8105c57476dfbf4c38