Unstable minisatellite expansion causing recessively inherited myoclonus epilepsy, EPM1

Nat Genet. 1997 Apr;15(4):393-6. doi: 10.1038/ng0497-393.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cystatin B
  • Cystatins / genetics*
  • Epilepsies, Myoclonic / genetics*
  • Female
  • Founder Effect
  • Humans
  • Male
  • Minisatellite Repeats / genetics*
  • Molecular Sequence Data
  • Mutation / genetics*
  • Polymorphism, Genetic
  • Promoter Regions, Genetic / genetics
  • Restriction Mapping

Substances

  • CSTB protein, human
  • Cystatins
  • Cystatin B

Associated data

  • GENBANK/U46692