Myoclonic Epilepsy of Unverricht and Lundborg (CSTB)
| Dred_ID | RD00031 |
| OMIM ID | 254800 |
| Disease name | Myoclonic Epilepsy of Unverricht and Lundborg |
| Alternative names | Uld Epilepsy, Progressive Myoclonic 1 Epm1 Progressive Myoclonic Epilepsy Pme Baltic Myoclonic Epilepsy Epilepsy, Progressive Myoclonic 1a Epm1a |
| Category | Genetic diseases, Rare diseases |
| Phenotype | NIH Rare Diseases: Progressive myoclonus epilepsy (PME) refers to a group of inherited conditions involving the central nervous system and representing more than a dozen different diseases. These diseases share certain features, including a worsening of symptoms over time and the presence of both muscle contractions (myoclonus) and seizures (epilepsy). PME is different from myoclonic epilepsy. Other features include dementia, dystonia, and trouble walking or speaking. These rare disorders often get worse over time and sometimes are fatal. Many of these PME diseases begin in childhood or adolescence.
OMIM: Myoclonic epilepsy of Unverricht and Lundborg is an autosomal recessive disorder characterized by onset of neurodegeneration between 6 and 13 years of age. Although it is considered a progressive myoclonic epilepsy, it differs from other forms in that is appears to be progressive only in adolescence, with dramatic worsening of myoclonus and ataxia in the first 6 years after onset. The disease stabilizes in early adulthood, and myoclonus and ataxia may even improve, and there is minimal to no cognitive decline (summary by Ramachandran et al., 2009). |
| Miscellaneouse | OMIM: onset 6-13 years three stages of disease progression - stage 1 (subclinical), stage 2 (early myoclonic), stage 3 (disabling myoclonic) incidence of 1 in 20,000 live births high frequency in finnish population |
| Prevalence | Progressive Myoclonic Epilepsy Type 1: 1-9/100000 (Finland) [source: MalaCards] |
| Inheritance | Autosomal recessive |
| Anticipation | N/A |
| Evidence | Weak |
| Gene symbol | CSTB |
| Alias symbols | PME; ULD; CST6; EPM1; STFB; EPM1A |
| Gene name | cystatin B |
| Gene map locus | 21q22.3; chr21:43,772,511-43,776,330(-) |
| Ensembl Gene ID | ENSG00000160213 |
| Gene expression and Gene Ontology | BioGPS |
| Protein expression | Human Protein Atlas |
| Gene sequence | Sequence |
| Variation | ClinVar, dbSNP | Gene conservation | Gene Conservation from UCSC Genome Browser |
| Gene Description | The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and kininogens. This gene encodes a stefin that functions as an intracellular thiol protease inhibitor. The protein is able to form a dimer stabilized by noncovalent forces, inhibiting papain and cathepsins l, h and b. The protein is thought to play a role in protecting against the proteases leaking from lysosomes. Evidence indicates that mutations in this gene are responsible for the primary defects in patients with progressive myoclonic epilepsy (EPM1). One type of mutation responsible for EPM1 is the expansion in the promoter region of this gene of a CCCCGCCCCGCG repeat from 2-3 copies to 30-78 copies. [provided by RefSeq, Jul 2016] |
| Repeat unit | CCCCGCCCCGCG |
| Normal repeat copies | 2-3 |
| Pathogenic repeat copies | ≥30 |
| Gene | CSTB |
| Repeat location | 5' UTR |
| Chromosome locus | NULL (-) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | RNA |
| Possible toxicity | We hypothesized that copy-number variation of sequence repeats contribute to the expression variation of some genes. Our laboratory has previously identified that the rare expansion of a repeat c.-174CGGGGCGGGGCG in the promoter region of the CSTB gene causes a silencing of the gene, resulting in progressive myoclonus epilepsy. [By PMID: 22573514] |
| Pathway annotation | Reactome, KEGG |
| PMID | 9054946 |
| Authors | Lafrenière RG, Rochefort DL, Chrétien N, Rommens JM, Cochius JI, Kälviäinen R, Nousiainen U, Patry G, Farrell K, Söderfeldt B, Federico A, Hale BR, Cossio OH, Sørensen T, Pouliot MA, Kmiec T, Uldall P, Janszky J, Pranzatelli MR, Andermann F, Andermann E, Rouleau GA |
| Title | Unstable insertion in the 5' flanking region of the cystatin B gene is the most common mutation in progressive myoclonus epilepsy type 1, EPM1 |
| Journal | Nat Genet. 15(3):298-302 |
| Year | 1997 |