Lafora progressive Myoclonus Epilepsy mutation database-EPM2A and NHLRC1 (EPM2B) genes
Leonarda Ianzano1, Junjun Zhang, Elayne M Chan
1Department of Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Abstract:
Progressive Myoclonus Epilepsy (PME) of the Lafora type is an autosomal recessive disease, which presents in teenage years with myoclonia and generalized seizures leading to death within a decade of onset. It is characterized by pathognomonic inclusions, Lafora bodies (LB), in neurons and other cell types. Two genes causing Lafora disease (LD), EPM2A on chromosome 6q24 and NHLRC1 (EPM2B) on chromosome 6p22.3 have been identified, and our recent results indicate there is at least one other gene causing the disease. The EPM2A gene product, laforin, is a protein tyrosine phosphatase (PTP) with a carbohydrate-binding domain (CBD) in the N-terminus. NHLRC1 encodes a protein named malin, containing a zinc finger of the RING type in the N-terminal half and 6 NHL-repeat domains in the C-terminal direction. To date 43 different variations in EPM2A and 23 in NHLRC1 are known, including missense, nonsense, frameshift, and deletions. We have developed a human LD mutation database using a new generic biological database cross-referencing platform. The database, which currently contains 66 entries is accessible on the World Wide Web (http://projects.tcag.ca/lafora). Entries can be submitted via the curator of the database or via a web-based form.
Insights
Lafora disease (LD), a type of Progressive Myoclonus Epilepsy (PME), is a severe genetic disorder. A new online database catalogs known mutations in LD genes, aiding research into this rare epilepsy.
Area of Science:
- Genetics and Molecular Biology
- Neurology
- Biochemistry
Background:
- Lafora disease (LD) is an autosomal recessive Progressive Myoclonus Epilepsy (PME) presenting in adolescence.
- Characterized by Lafora bodies (LB) in neurons, LD leads to fatal neurodegeneration within a decade.
- Known causative genes include EPM2A (laforin) and NHLRC1 (malin); however, other genes likely contribute.
Purpose of the Study:
- To develop a comprehensive human Lafora disease mutation database.
- To provide a centralized, accessible resource for researchers studying LD genetics.
- To facilitate the submission and curation of new genetic variations.
Main Methods:
- Utilized a generic biological database cross-referencing platform.
- Developed a web-accessible database for Lafora disease mutations.
- Implemented a curator-based and web-based submission system for new entries.
Main Results:
- Created a human LD mutation database with 66 entries.
- The database is publicly accessible via the World Wide Web.
- Established a system for ongoing data submission and updates.
Conclusions:
- The developed database serves as a valuable resource for Lafora disease research.
- Centralizing mutation data aids in understanding LD pathogenesis and genetic heterogeneity.
- The accessible platform promotes collaborative research and data sharing.
