Unstable minisatellite expansion causing recessively inherited myoclonus epilepsy, EPM1

Academic Article


  • Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1; MIM 254800) is an autosomal recessive disorder that occurs with a low frequency in many populations but is more common in Finland and the Mediterranean region. It is characterized by stimulus-sensitive myoclonus and tonic-clonic seizures with onset at age 6-15 years, typical electroencephalographic abnormalities and a variable rate of progression between and within families. Following the initial mapping of the EPM1 gene to chromosome 21 (ref. 6) and the refinement of the critical region to a small interval, positional cloning identified the gene encoding cystatin B (CST6), a cysteine protease inhibitor, as the gene underlying EPM1 (ref. 10). Levels of messenger RNA encoded by CST6 were dramatically decreased in patients. A 3' splice site and a stop codon mutation were identified in three families, leaving most mutations uncharacterized. In this study, we report a novel type of disease- causing mutation, an unstable 15- to 18-mer minisatellite repeat expansion in the putative promoter region of the CST6 gene. The mutation accounts for the majority of EPM1 patients worldwide. Haplotype data are compatible with a single ancestral founder mutation. The length of the repeat array differs between chromosomes and families, but changes in repeat number seem to be comparatively rare events.
  • Published In

  • Nature Genetics  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 19047844
  • Author List

  • Virtaneva K; D'Amato E; Miao J; Koskiniemi M; Norio R; Avanzini G; Franceschetti S; Michelucci R; Tassinari CA; Omer S
  • Start Page

  • 393
  • End Page

  • 396
  • Volume

  • 15
  • Issue

  • 4