Lafora progressive myoclonus epilepsy: A meta-analysis of reported mutations in the first decade following the discovery of the EPM2A and NHLRC1 genes
Article first published online: 6 MAR 2009
© 2009 Wiley-Liss, Inc.
Volume 30, Issue 5, pages 715–723, May 2009
How to Cite
Singh, S. and Ganesh, S. (2009), Lafora progressive myoclonus epilepsy: A meta-analysis of reported mutations in the first decade following the discovery of the EPM2A and NHLRC1 genes. Hum. Mutat., 30: 715–723. doi: 10.1002/humu.20954
- Issue published online: 27 APR 2009
- Article first published online: 6 MAR 2009
- Manuscript Accepted: 18 NOV 2008
- Manuscript Received: 15 JUL 2008
- Department of Science and Technology, Department of Biotechnology, and Board of Radiation and Nuclear Sciences, Government of India
- Council of Scientific and Industrial Research (New Delhi)
- locus heterogeneity;
- inclusion bodies;
Lafora disease (LD) is an autosomal recessive and fatal form of progressive myoclonus epilepsy. LD patients manifest myoclonus and tonic–clonic seizures, visual hallucinations, and progressive neurologic deterioration beginning at 12 to 15 years of age. The two genes known to be associated with LD are EPM2A and NHLRC1. Mutations in at least one other as yet unknown gene also cause LD. The EMP2A encodes a protein phosphatase and NHLRC1 encodes an ubiquitin ligase. These two proteins interact with each other and, as a complex, are thought to regulate critical neuronal functions. Nearly 100 distinct mutations have been discovered in the two genes in over 200 independent LD families. Nearly half of them are missense mutations, and the deletion mutations account for one-quarter. Several reports have provided functional data for the mutant proteins and a few also provide genotype–phenotype correlations. In this review we provide an update on the spectrum of EPM2A and NHLRC1 mutations, and discuss their distribution in the patient population, genotype–phenotype correlations, and on the possible effect of disease mutations on the cellular functions of LD proteins. Hum Mutat 0, 1–9, 2009. © 2009 Wiley-Liss, Inc.