Microdeletions involving the SCN1A gene may be common in SCN1A-mutation-negative SMEI patients†

摘要: Severe myoclonic epilepsy of infancy (SMEI) or Dravet syndrome is a rare syndrome. In 30 to 70% SMEI patients, truncating and missense mutations in the neuronal voltage-gated sodium-channel α-subunit gene (SCN1A) have been identified. The majority patients that are predicted be loss-of-function alleles. Because mutation detection studies use PCR-based sequencing conformation sensitive gel electrophoresis (CSGE), microdeletions, which also alleles, can easily escape detection. We selected 11 with without additional features who had no SCN1A detectable analysis. addition, none was heterozygous for any SNPs SCN1A, indicating they were either homozygous all hemizygous due microdeletion gene. subsequently analyzed these presence microdeletions using quantitative PCR method named multiplex amplicon quantification (MAQ), observed three missing one copy All confirmed by fluorescence situ hybridization (FISH). These findings demonstrate substantial percentage SCN1A-mutation-negative carry chromosomal comprising haploinsufficiency cause SMEI. Hum Mutat 27(9), 914–920, 2006. © 2006 Wiley-Liss, Inc.