Unstable minisatellite expansion causing recessively inherited myoclonus epilepsy, EPM1

Kimmo Virtaneva, Elena D'Amato, Jinmin Miao, Marjaleena Koskiniemi, Reijo Norio, Giuliano Avanzini, Silvana Franceschetti, Roberto Michelucci, Carlo A. Tassinari, Salah Omer, Len A. Pennacchio, Richard M. Myers, José L. Dieguez-Lucena, Ralf Krahe, Albert De La Chapelle, Anna Elina Lehesjoki

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)393-396
Number of pages4
JournalNature Genetics
Issue number4
Publication statusPublished - Apr 1997

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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