title: Mutation of a potassium channel-related gene in progressive myoclonic epilepsy.
abstract: OBJECTIVE
  We investigated a large consanguineous Moroccan family with progressive myoclonic epilepsy (PME) consistent with autosomal recessive inheritance, to describe the phenotype and identify the causal gene.
  
  
  METHODS
  We recorded the clinical course of the disease and the response to drug therapy, whereas carefully excluding known causes of progressive myoclonic epilepsy. We then linked the disease by homozygosity mapping using microsatellite markers and single nucleotide polymorphism microarrays (11K GeneChip), and studied candidate genes in the critical linkage region.
  
  
  RESULTS
  Epilepsy started between 16 and 24 months of age after normal initial development. Seizures were multifocal myoclonus aggravated by movements, and generalized tonic-clonic seizures were experienced by two patients. Electroencephalogram showed slow dysrhythmia, multifocal and occasionally generalized epileptiform discharges, and photosensitivity. Brain magnetic resonance images were normal. All patients were demented. Two had refractory epilepsy and a severe course. Seizures were controlled in the third patient, whose disease course was less severe. Linkage analyses identified a new locus on 7q11.2, with a maximum multipoint logarithm of odds of 4.0 at D7S663. In the critical linkage region, we found a C to T mutation in exon 2 of the potassium channel tetramerization domain containing 7 gene (KCTD7). The mutation affected a highly conserved segment of the predicted protein, changing an arginine codon into a stop codon (R99X).
  
  
  CONCLUSIONS
  Neurodegeneration in progressive myoclonic epilepsy presented by our patients paralleled the refractoriness of epilepsy. The disease was transmitted as an autosomal recessive trait linked to a novel locus at 7q11.2, where we identified a mutation in KCTD7.
authors: Department of Pediatric Neurology, Université Libre de Bruxelles, Hôpital Erasme, Brussels, Belgium. pvanboga@ulb.ac.be
authors: Patrick
authors: P
authors: Van Bogaert
authors: Regis
authors: R
authors: Azizieh
authors: Julie
authors: J
authors: Désir
authors: Alec
authors: A
authors: Aeby
authors: Linda
authors: L
authors: De Meirleir
authors: Jean-François
authors: JF
authors: Laes
authors: Florence
authors: F
authors: Christiaens
authors: Marc J
authors: MJ
authors: Abramowicz
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D018450:Disease Progression; D004831:Epilepsies, Myoclonic / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009018:Morocco; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D015221:Potassium Channels / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: C522280:KCTD7 protein, human; D015221:Potassium Channels