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 region1,2. 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 families3–5. Following the initial mapping of the EPM1 gene to chromosome 21 (ref. 6) and the refinement of the critical region to a small interval7–9, positional cloning identified the gene encoding cystatin B (C5T6), 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 uncharacterized10. 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.
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Virtaneva, K., D'Amato, E., Miao, J. et al. Unstable minisatellite expansion causing recessively inherited myoclonus epilepsy, EPM1. Nat Genet 15, 393–396 (1997). https://doi.org/10.1038/ng0497-393
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DOI: https://doi.org/10.1038/ng0497-393
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