title: A cohort study of pyridoxine-dependent epilepsy and high prevalence of splice site IVS11+1G>A mutation in Chinese patients.
abstract: OBJECTIVE
  Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disorder caused by mutations of the ALDH7A1 gene. We aimed to analyze the relations between the clinical diagnosis and treatment of PDE and ALDH7A1 gene mutations in Chinese PDE patients.
  
  
  METHODS
  The clinical manifestations, diagnosis and treatment were observed in a cohort of PDE patients with early onset of seizure. Video-electroencephalogram (VEEG) and magnetic resonance imaging (MRI) were performed. The mutation of ALDH7A1 gene was analyzed.
  
  
  RESULTS
  Of eight patients, six were males and two were females. Age of seizure onset ranged from 1 to 100 days and 75% patients presented with seizures in the neonatal period. All patients showed different degrees of developmental delay. EEGs showed focal or multifocal discharges, or were normal. Molecular analysis revealed 10 ALDH7A1 mutations, including 2 splice site mutations. Five patients had mutation at IVS11+1G>A site, six patients had missense mutations, one with nonsense mutation and another patient had 9-bp genomic deletion mutation. Among them, two mutations were first time reported.
  
  
  CONCLUSIONS
  Seizure onset was in neonatal or early infantile period in our PDE patients. Early recognition and diagnosis of the disease is necessary for early intervention and improve cognitive development in the later life. In this study, on the molecular level, we also identified the splice site mutation IVS11+1G>A as a high prevalence mutation site with a frequency of 31.25% (5 of 16 alleles) in Chinese PDE patients.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China. Electronic address: xuejiao2277@163.com.
authors.forename: Jiao
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China. Electronic address: qianpingerke@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Qian
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China. Electronic address: lihui1409@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China. Electronic address: dryewu@263.net.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China. Electronic address: dr_lxy@sina.com.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China. Electronic address: zhixian.yang@163.com.
authors.forename: Zhixian
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000143:Acids / Q000652:urine; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000596:Amino Acids / Q000097:blood; D044466:Asian People / Q000235:genetics; D002675:Child, Preschool; D015331:Cohort Studies; D004569:Electroencephalography; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000652:urine; D005260:Female; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D015995:Prevalence; D011736:Pyridoxine / Q000627:therapeutic use; D014741:Video Recording; D014803:Vitamin B Complex / Q000627:therapeutic use
chemical_list: D000143:Acids; D000596:Amino Acids; D014803:Vitamin B Complex; C089507:ALDH7A1 protein, human; D000444:Aldehyde Dehydrogenase; D011736:Pyridoxine
keywords: ALDH7A1 gene; Antiquitin; High prevalence mutation; Pyridoxine-dependent epilepsy