Document Detail

The epilepsy, the protease inhibitor and the dodecamer: progressive myoclonus epilepsy, cystatin b and a 12-mer repeat expansion.
MedLine Citation:
PMID:  14526183     Owner:  NLM     Status:  MEDLINE    
Progressive myoclonus epilepsy 1 (EPM1) or Unverricht-Lundborg disease is a human autosomal recessive neurodegenerative disorder caused by mutations in cystatin B (CSTB). The CSTB gene maps to human chromosome 21 and encodes an inhibitor of lysosomal cysteine proteases. Five point mutations have been found, two of which are seen in numerous unrelated patients. However, the main CSTB mutation in EPM1, even among patients of different ethnic origins, is an expansion of a dodecamer repeat (CCCCGCCCCGCG) in the 5' flanking area of CSTB. Most normal alleles contain either two or three repeats, while rarer normal alleles that are highly unstable contain between 12 and 17 repeats. Mutant expanded alleles have been reported to contain between 30 and 80 copies and are also highly unstable, particularly via parental transmission. There is no apparent correlation between mutant repeat length and disease phenotype. While the repeat expansion is outside the CSTB transcriptional unit, it results in a marked decrease in CSTB expression, at least in certain cell types in vitro. CSTB homozygous knockout mice show some parallels to the phenotype of human EPM1 including myoclonic seizures, development of ataxia and neuropathological changes associated with cell loss via apoptosis. Loss of CSTB function due to mutations is consistent with the observed neurodegenerative pathology and phenotype, but the functional link to the epileptic phenotype of EPM1 remains largely unknown.
M D Lalioti; S E Antonarakis; H S Scott
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Cytogenetic and genome research     Volume:  100     ISSN:  1424-859X     ISO Abbreviation:  Cytogenet. Genome Res.     Publication Date:  2003  
Date Detail:
Created Date:  2003-10-03     Completed Date:  2004-01-30     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  101142708     Medline TA:  Cytogenet Genome Res     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  213-23     Citation Subset:  IM    
Copyright Information:
Copyright 2003 S. Karger AG, Basel
Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
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MeSH Terms
Base Sequence
Cystatin B
Cystatins / genetics*
Cysteine Proteinase Inhibitors / genetics
DNA Repeat Expansion / genetics*
Family Health
Gene Expression Regulation
Minisatellite Repeats / genetics*
Myoclonic Epilepsies, Progressive / genetics*,  pathology
Polymorphism, Genetic
Reg. No./Substance:
0/CSTB protein, human; 0/Cstb protein, mouse; 0/Cystatins; 0/Cysteine Proteinase Inhibitors; 88844-95-5/Cystatin B

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