Instability of the EPM1 Minisatellite

Inherited mutations in the cystatin B gene (CSTB) are responsible for progressive myoclonus epilepsy type 1 (EPM1; MIM 254800). This autosomal recessive disease is characterized by variable progression to mental retardation, dementia and ataxia. The majority of EPM1 alleles identified to date contai...

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Bibliographic Details
Published in:Human molecular genetics 1999-10, Vol.8 (11), p.1985-1988
Main Authors: Larson, Garry P., Ding, Shaofeng, Lafrenière, Ronald G., Rouleau, Guy A., Krontiris, Theodore G.
Format: Article
Language:English
Subjects:
Alleles
Biological and medical sciences
Classical genetics, quantitative genetics, hybrids
CSTB gene
Cystatin B
Cystatins - genetics
Epilepsies, Myoclonic - genetics
Female
Fundamental and applied biological sciences. Psychology
Genes, ras
Genetics of eukaryotes. Biological and molecular evolution
Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy
Human
Humans
Male
Medical sciences
Meiosis
Minisatellite Repeats
minisatellites
Nervous system (semeiology, syndromes)
Neurology
Pedigree
Polymerase Chain Reaction
progressive myoclonus epilepsy 1
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Summary:Inherited mutations in the cystatin B gene (CSTB) are responsible for progressive myoclonus epilepsy type 1 (EPM1; MIM 254800). This autosomal recessive disease is characterized by variable progression to mental retardation, dementia and ataxia. The majority of EPM1 alleles identified to date contain expansions of a dodecamer repeat located upstream of the transcription start site of the CSTB gene. Normal alleles contain two or three copies of the repeat, whereas pathogenic alleles contain >40 repeats. We examined the meiotic stability of pathogenic, expanded EPM1 alleles from 17 EPM1 families by employing a fluorescence-based PCR-based genotyping assay capable of detecting single dodecamer repeat unit differences on an automated DNA sequencer. We followed 74 expanded allele transmissions to 30 affected individuals and 22 carriers. Thirty-five of 74 expanded allele transmissions demonstrated either contraction or expansion of the minisatellite, typically by a single repeat unit. Thus expanded alleles of the EPM1 minisatellite demonstrate a mutation rate of 47%, the highest yet observed for pathogenetic alleles of a human minisatellite.
ISSN:0964-6906
1460-2083
1460-2083
DOI:10.1093/hmg/8.11.1985