Referenced in: none

Automatically associated channels: Kv2.1

Title: Microchromosomal deletions involving SCN1A and adjacent genes in severe myoclonic epilepsy in infancy.

Authors: Ji-wen Wang, Hirokazu Kurahashi, Atsushi Ishii, Toshio Kojima, Masaharu Ohfu, Takahito Inoue, Atsushi Ogawa, Sawa Yasumoto, Hirokazu Oguni, Shigeo Kure, Tatsuya Fujii, Masatoshi Ito, Takehiko Okuno, Yukiyoshi Shirasaka, Jun Natsume, Aki Hasegawa, Akihiko Konagaya, Sunao Kaneko, Shinichi Hirose

Journal, date & volume: Epilepsia, 2008 Sep , 49, 1528-34

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18479393

Abstract
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.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.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.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.