PMID- 16865694
OWN - NLM
STAT- MEDLINE
DCOM- 20061024
LR  - 20121115
IS  - 1098-1004 (Electronic)
IS  - 1059-7794 (Linking)
VI  - 27
IP  - 9
DP  - 2006 Sep
TI  - Microdeletions involving the SCN1A gene may be common in SCN1A-mutation-negative 
      SMEI patients.
PG  - 914-20
AB  - 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.
CI  - (c) 2006 Wiley-Liss, Inc.
FAU - Suls, Arvid
AU  - Suls A
AD  - Neurogenetics Group, Department of Molecular Genetics, Flanders Interuniversity 
      Institute for Biotechnology (VIB), University of Antwerp, Antwerp, Belgium.
FAU - Claeys, Kristl G
AU  - Claeys KG
FAU - Goossens, Dirk
AU  - Goossens D
FAU - Harding, Boris
AU  - Harding B
FAU - Van Luijk, Rob
AU  - Van Luijk R
FAU - Scheers, Stefaan
AU  - Scheers S
FAU - Deprez, Liesbet
AU  - Deprez L
FAU - Audenaert, Dominique
AU  - Audenaert D
FAU - Van Dyck, Tine
AU  - Van Dyck T
FAU - Beeckmans, Sabine
AU  - Beeckmans S
FAU - Smouts, Iris
AU  - Smouts I
FAU - Ceulemans, Berten
AU  - Ceulemans B
FAU - Lagae, Lieven
AU  - Lagae L
FAU - Buyse, Gunnar
AU  - Buyse G
FAU - Barisic, Nina
AU  - Barisic N
FAU - Misson, Jean-Paul
AU  - Misson JP
FAU - Wauters, Jan
AU  - Wauters J
FAU - Del-Favero, Jurgen
AU  - Del-Favero J
FAU - De Jonghe, Peter
AU  - De Jonghe P
FAU - Claes, Lieve R F
AU  - Claes LR
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 0 (Codon, Nonsense)
RN  - 0 (NAV1.1 Voltage-Gated Sodium Channel)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (SCN1A protein, human)
RN  - 0 (Sodium Channels)
SB  - IM
MH  - Child
MH  - Chromosome Mapping
MH  - Codon, Nonsense
MH  - DNA Mutational Analysis
MH  - Epilepsies, Myoclonic/diagnosis/*genetics
MH  - Female
MH  - *Gene Deletion
MH  - Genetic Testing/methods
MH  - Haplotypes
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Infant
MH  - Male
MH  - Mutation, Missense
MH  - NAV1.1 Voltage-Gated Sodium Channel
MH  - Nerve Tissue Proteins/*genetics
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single Nucleotide
MH  - Sodium Channels/*genetics
EDAT- 2006/07/26 09:00
MHDA- 2006/10/25 09:00
CRDT- 2006/07/26 09:00
PHST- 2006/07/26 09:00 [pubmed]
PHST- 2006/10/25 09:00 [medline]
PHST- 2006/07/26 09:00 [entrez]
AID - 10.1002/humu.20350 [doi]
PST - ppublish
SO  - Hum Mutat. 2006 Sep;27(9):914-20. doi: 10.1002/humu.20350.