title: Frameshift mutations of the ARX gene in familial Ohtahara syndrome.
abstract: OBJECTIVE
  Ohtahara syndrome is one of the most severe and earliest forms of epilepsy and is frequently associated with brain malformations, such as hemimegalencephaly. Recently, longer expansion of the first polyalanine tract of ARX was found to be causative for Ohtahara syndrome without brain malformation, whereas premature termination mutations of ARX were found to cause severe brain malformations, such as lissencephaly or hydranencephaly. Both are designated as ARX-related interneuronopathies.
  
  
  METHODS
  We investigated the molecular basis of Ohtahara syndrome in two families, comprising six male patients in two generations demonstrating X-linked inheritance.
  
  
  RESULTS
  Novel frameshift mutations in the terminal exon of the ARX gene (Ala524fsX534 and E536fsX672) were identified in two patients (2 and 13 years, each) from both families. Two patients developed West syndrome, and one of these later developed Lennox-Gastaut syndrome. Brain magnetic resonance imaging (MRI) of all patients showed no brain malformations in contrast to the patients with a premature termination mutation in other exons of ARX.
  
  
  CONCLUSIONS
  The etiology of Ohtahara syndrome is heterogeneous; however, the molecular analysis of ARX should be considered in sporadic or familial male patients with Ohtahara syndrome.
authors.affiliation: Department of Pediatrics, Yamagata University Faculty of Medicine, Iida-nishi, Yamagata, Japan. mkato@med.id.yamagata-u.ac.jp
authors.forename: Mitushiro
authors.initials: M
authors.lastname: Kato
authors.forename: Norihisa
authors.initials: N
authors.lastname: Koyama
authors.forename: Masayasu
authors.initials: M
authors.lastname: Ohta
authors.forename: Kiyokuni
authors.initials: K
authors.lastname: Miura
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hayasaka
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology; D001921:Brain / Q000002:abnormalities* / Q000473:pathology; D002648:Child; D004569:Electroencephalography / Q000706:statistics & numerical data; D004827:Epilepsy / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D005091:Exons / Q000235:genetics; D005190:Family / Q000523:psychology; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D050172:Genes, X-Linked / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007395:Interneurons / Q000473:pathology; D007888:Leigh Disease / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011247:Pregnancy; D013036:Spasms, Infantile / Q000235:genetics / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C469264:ARX protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors