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Microchromosomal deletions involving SCN1A and adjacent genes in severe myoclonic epilepsy in infancy
Author(s) -
Wang Jiwen,
Kurahashi Hirokazu,
Ishii Atsushi,
Kojima Toshio,
Ohfu Masaharu,
Inoue Takahito,
Ogawa Atsushi,
Yasumoto Sawa,
Oguni Hirokazu,
Kure Shigeo,
Fujii Tatsuya,
Ito Masatoshi,
Okuno Takehiko,
Shirasaka Yukiyoshi,
Natsume Jun,
Hasegawa Aki,
Konagaya Akihiko,
Kaneko Sunao,
Hirose Shinichi
Publication year - 2008
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2008.01609.x
Subject(s) - myoclonic epilepsy , multiplex ligation dependent probe amplification , genetics , comparative genomic hybridization , phenotype , biology , medicine , epilepsy , gene , exon , chromosome , neuroscience
SummaryPurpose: Genetic abnormalities of the gene encoding α1 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.Discussion: 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.