title: Microchromosomal deletions involving SCN1A and adjacent genes in severe myoclonic epilepsy in infancy.
abstract: OBJECTIVE
  Genetic abnormalities of the gene encoding alpha1 subunit of the sodium channel (SCN1A), which can be detected by direct sequencing, are present in more than 60% of patients with severe myoclonic epilepsy in infancy (SMEI) or its borderline phenotype (SMEB). Microchromosomal deletions have been recently reported as additional causes of SMEI. This study examines whether such microdeletions are associated with SMEI as well as with SMEB.
  
  
  METHODS
  We recruited patients with SMEI (n = 35) and SMEB (n = 34), who were confirmed previously to have no mutations of SCN1A by direct sequencing. Microdeletions were sought by multiplex ligation-dependent probe amplification (MLPA), and then confirmed and characterized by fluorescence in situ hybridization (FISH) and array-based comparative genomic hybridization (aCGH), respectively.
  
  
  RESULTS
  Heterozygous multiple exonic deletions were identified in 7/35 SMEI patients (20%) and 0/34 SMEB patients (0%), with a net frequency of 10.1% (7/69 patients). Deletions were confirmed by FISH and aCGH analysis. The concomitant deletions of adjacent genes were revealed by aCGH. None of the parents who agreed to undergo the analysis had such deletions suggesting that the deletions were de novo. The phenotypes of patients with the deletions were indistinguishable from those of SMEI resulting from point mutations.
  
  
  CONCLUSIONS
  Our findings indicate that microchromosomal deletion, often involving not only SCN1A but also several adjacent genes, is associated with core SMEI. As microchromosomal deletion cannot be anticipated by the phenotypes or detected by conventional methods, genetic abnormalities in SMEI should be carefully sought by techniques that can detect microdeletions.
authors.affiliation: Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Ji-wen
authors.initials: JW
authors.lastname: Wang
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kurahashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ishii
authors.forename: Toshio
authors.initials: T
authors.lastname: Kojima
authors.forename: Masaharu
authors.initials: M
authors.lastname: Ohfu
authors.forename: Takahito
authors.initials: T
authors.lastname: Inoue
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ogawa
authors.forename: Sawa
authors.initials: S
authors.lastname: Yasumoto
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Oguni
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kure
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fujii
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ito
authors.forename: Takehiko
authors.initials: T
authors.lastname: Okuno
authors.forename: Yukiyoshi
authors.initials: Y
authors.lastname: Shirasaka
authors.forename: Jun
authors.initials: J
authors.lastname: Natsume
authors.forename: Aki
authors.initials: A
authors.lastname: Hasegawa
authors.forename: Akihiko
authors.initials: A
authors.lastname: Konagaya
authors.forename: Sunao
authors.initials: S
authors.lastname: Kaneko
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirose
mesh_terms: D001921:Brain / Q000503:physiopathology; D002648:Child; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D004831:Epilepsies, Myoclonic / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns / Q000235:genetics; D008297:Male; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels