title: Instability of the EPM1 minisatellite.
abstract: 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.
authors.affiliation: Division of Molecular Medicine, Beckman Research Institute, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA.
authors.forename: G P
authors.initials: GP
authors.lastname: Larson
authors.forename: S
authors.initials: S
authors.lastname: Ding
authors.forename: R G
authors.initials: RG
authors.lastname: Lafrenière
authors.forename: G A
authors.initials: GA
authors.lastname: Rouleau
authors.forename: T G
authors.initials: TG
authors.lastname: Krontiris
mesh_terms: D000483:Alleles; D055313:Cystatin B; D015891:Cystatins / Q000235:genetics*; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D008540:Meiosis; D018598:Minisatellite Repeats; D010375:Pedigree; D016133:Polymerase Chain Reaction
chemical_list: C524994:CSTB protein, human; D015891:Cystatins; D055313:Cystatin B