Molecular aspects of Dravet syndrome patients in Taiwan
Journal
Clinica Chimica Acta
Journal Volume
421
Pages
34-40
Date Issued
2013
Author(s)
Lin W.-D.
Chang K.-P.
Wang C.-H.
Chen S.-J.
Lin W.-C.
Tsai Y.
Tsai C.-H.
Chou I.-C.
Tsai F.-J.
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. Conclusion: 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. ? 2013 Elsevier B.V.
SDGs
Other Subjects
4 aminobutyric acid A receptor gamma2; DNA; ephrin receptor A5; sodium channel Nav1.1; sodium channel Nav1.2; voltage gated sodium channel beta 1 subunit; article; child; clinical article; controlled study; copy number variation; disease classification; DNA microarray; DNA sequence; EPHA5 gene; exon; female; frameshift mutation; GABRD gene; GABRG2 gene; gene; genetic variability; human; intron; male; medical history; microarray analysis; missense mutation; neurologic examination; nucleotide sequence; preschool child; priority journal; school child; SCN1A gene; SCN1B gene; SCN2A gene; severe myoclonic epilepsy in infancy; single nucleotide polymorphism; Taiwan; Amino Acid Sequence; Child; Child, Preschool; DNA Copy Number Variations; DNA Mutational Analysis; Epilepsies, Myoclonic; Exons; Female; Humans; Introns; Male; Microarray Analysis; Molecular Sequence Data; Mutation; NAV1.1 Voltage-Gated Sodium Channel; Polymorphism, Single Nucleotide; Receptor, EphA5; Taiwan
Type
journal article