Abstract
Lafora progressive myoclonus epilepsy is characterized by pathognomonic endoplasmic reticulum (ER)-associated polyglucosan accumulations. We previously discovered that mutations in EPM2A cause Lafora disease. Here, we identify a second gene associated with this disease, NHLRC1 (also called EPM2B), which encodes malin, a putative E3 ubiquitin ligase with a RING finger domain and six NHL motifs. Laforin and malin colocalize to the ER, suggesting they operate in a related pathway protecting against polyglucosan accumulation and epilepsy.
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Acknowledgements
We thank members of The Centre for Applied Genomics (http://tcag.bioinfo.sickkids.on.ca/) for assistance, notably A. Paterson and D. Bulman; the families with Lafora disease for support; and L. Palm, A. Prasad, D. Buckley, T. Minett, W. Bara-Jimenez, L. Jardim and J.M. Saraiva, who contributed single cases. This work was funded by the Canadian Institutes of Health Research, the Canadian Genetic Diseases Network, Genome Canada and the Hospital for Sick Children Foundation. L.I. is supported by the Comitato Telethon Fondazione Onlus. S.W.S. is an Investigator of CIHR and International Scholar of the Howard Hughes Medical Institute.
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Chan, E., Young, E., Ianzano, L. et al. Mutations in NHLRC1 cause progressive myoclonus epilepsy. Nat Genet 35, 125–127 (2003). https://doi.org/10.1038/ng1238
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DOI: https://doi.org/10.1038/ng1238
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