title: Molecular aspects of Dravet syndrome patients in Taiwan.
abstract: BACKGROUND
  Dravet syndrome (DS) is a rare form of intractable epilepsy. Children with DS often start having seizures in infancy, and gradually develop other seizure types. Several studies have demonstrated that certain gene mutations and submicroscopic copy number variations (CNV) in DS patients are strongly associated with intractable epilepsy. In this study, directed DNA sequencing and microarray technology were used to investigate genomic variations in DS patients.
  
  
  METHODS
  A total of nine DS patients were enrolled in this genetic study. A detailed medical history was obtained from each participant, and appropriate neurological examinations performed. Seizure types and epilepsy syndromes were classified according to ILAE criteria. The complete coding regions of SCN1A, SCN1B, SCN2A, GABRG2, and GABRD, including the intron/exon boundaries, were sequenced using DNA samples drawn from participants. In addition, whole genome CNV analysis was conducted via SNP microarray analysis.
  
  
  RESULTS
  DNA sequencing revealed a mutation in the SCN1A gene in five (55.6%) of the DS patients, within which three missense mutations, c.719T>C (p.Leu240Pro), c.2807A>T (p.Asp936Val), c.4349A>C (p.Gln1450Pro), and two frameshift mutations, c.2277insAACA (p.His759fsX772) and c.3972insT (p.Leu1324fsX1331) were observed. Upon CNV analysis, a novel duplication region, 4q13.1-q13.2, was detected in one DS patient; this variant region contained a gene, EPHA5, related to cerebral neuron development.
  
  
  CONCLUSIONS
  This study extended the spectrum of SCN1A mutations in Taiwanese DS patients and confirms the high sensitivity of SCN1A for the DS phenotype. In addition, a novel duplication region identified within EPHA5 should be considered in future screening procedures for DS.
authors.affiliation: Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Wei-De
authors.initials: WD
authors.lastname: Lin
authors.forename: Kai-Ping
authors.initials: KP
authors.lastname: Chang
authors.forename: Chung-Hsing
authors.initials: CH
authors.lastname: Wang
authors.forename: Shyi-Jou
authors.initials: SJ
authors.lastname: Chen
authors.forename: Pi-Chuan
authors.initials: PC
authors.lastname: Fan
authors.forename: Wen-Chin
authors.initials: WC
authors.lastname: Weng
authors.forename: Wei-Chiang
authors.initials: WC
authors.lastname: Lin
authors.forename: Yushin
authors.initials: Y
authors.lastname: Tsai
authors.forename: Chang-Hai
authors.initials: CH
authors.lastname: Tsai
authors.forename: I-Ching
authors.initials: IC
authors.lastname: Chou
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
mesh_terms: D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D004831:Epilepsies, Myoclonic / Q000175:diagnosis / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D007438:Introns; D008297:Male; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D009154:Mutation; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D036123:Receptor, EphA5 / Q000235:genetics*; D013624:Taiwan
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human; C484173:EPHA5 protein, human; D036123:Receptor, EphA5