title: Clinical and genetic analysis of three Korean children with pyridoxine-dependent epilepsy.
abstract: Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disorder that causes intractable seizures, especially in neonates and infants. Patients are typically resistant to typical antiepileptic drugs (AEDs) but respond dramatically to pyridoxine. Mutations in the ALDH7A1 gene are associated with the pathogenesis of PDE. Herein, we report the clinical phenotypes and disease-causative mutations in the ALDH7A1 gene in three Korean patients with PDE. We reviewed the medical records, electroencephalography (EEG), brain magnetic resonance imaging (MRI) findings, and the results of molecular genetic tests for the patients who were diagnosed with PDE in our institution between Jan. 1996 and Dec. 2010. In all patients, the first seizures began during the first week of life. The seizures were not fully controlled with multiple AEDs, but disappeared immediately after administration of pyridoxine and returned after it was transiently discontinued. Before the use of pyridoxine, interictal EEGs showed multifocal epileptiform discharges, which became normalized with pyridoxine. Direct sequencing analyses revealed two mutant alleles in all three patients. Patient 1 was compound heterozygous with two different missense mutations, c.1061A>G (p.Y354C) and c.1232C>T (p.P411L). Patient 2 was homozygous for a missense mutation, c.1279G>C (p.E427Q). Patient 3 was compound heterozygous for two different missense mutations, c.1061A>G (p.Y354C) and c.1279G>C (p.E427Q), and her parents and younger brother were heterozygous carriers of each one of the mutations. All three mutations had not previously been reported. Herein, we report three Korean patients with three novel mutations who presented with PDE.
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, Korea.
authors.forename: Sook Hyun
authors.initials: SH
authors.lastname: Nam
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kwon
authors.forename: Jeehun
authors.initials: J
authors.lastname: Lee
authors.forename: Cha Gon
authors.initials: CG
authors.lastname: Lee
authors.forename: Hee Joon
authors.initials: HJ
authors.lastname: Yu
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.forename: Munhyang
authors.initials: M
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000444:Aldehyde Dehydrogenase / Q000737:chemistry / Q000235:genetics; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D004827:Epilepsy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D056910:Republic of Korea; D016415:Sequence Alignment
chemical_list: D004247:DNA; C089507:ALDH7A1 protein, human; D000444:Aldehyde Dehydrogenase