Title: Microdeletions involving the SCN1A gene may be common in SCN1A-mutation-negative SMEI patients
Authors: Suls, Arvid ×
Claeys, Kristl
Goossens, D
Harding, Boris
Van Luijk, Rob
Scheers, Stefaan
Deprez, Liesbet
Audenaert, Dominique
Van Dyck, Tine
Beeckmans, Sabine
Smouts, Iris
Ceulemans, Berten
Lagae, Lieven
Buyse, Gunnar
Barisic, Nina
Misson, Jean-Paul
Wauters, Jan
Del-Favero, Jurgen
De Jonghe, Peter
Claes, Lieve R F #
Issue Date: Sep-2006
Publisher: Wiley-liss
Series Title: Human mutation vol:27 issue:9 pages:914-20
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 alpha-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.
ISSN: 1059-7794
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Muscle Diseases and Neuropathies
Brain & Metabolism Section (-)
× corresponding author
# (joint) last author

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