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GENATLAS PHENOTYPE
last update : 12-03-2015
Symbol EPM2A
Location 6q24.3
Name myoclonic epilepsy, progressive, Lafora type 2A
Corresponding gene EPM2A
Main clinical features
  • early symptoms in the teenage years
  • associated with progressive neurological deterioration and glycogen-like intracellular inclusion bodies (presence of periodic acid-Schiff (PAS) positive Lafora inclusion bodies present primarily in neuronal perikarya and dendrites, but also found in other organs) similar to the polysaccharide that accumulates in branching enzyme deficiency (GBE1)
  • accumulation of polyglucosan inclusion bodies, called Lafora bodies, in the cytoplasm of cells in the central nervous system and in many other organs (PMID: 20453062))
  • hallmark of the disease is the presence in skeletal muscle and brain of intracellular inclusions known as Lafora bodies (LB), the main constituent of which is polyglucosan (PMID: 18852261))
  • accumulation of glycogen-like intracellular inclusions named Lafora bodies in many organs such as the brain, liver, heart, skeletal muscle and skin (PMID: 20858601))
    • Genetic determination autosomal recessive
    Prevalence 50p 100 of the cases of Lafora disease result from mutations in the EPM2A gene
    Function/system disorder neurology
    Type disease
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    various types   truncated protein predominantly truncating mutation
    Remark(s)
  • mutations affecting the phosphatase domain are more likely to form aggregates
  • excessive phosphorylation of glycogen can impair branching, by a yet-to-be-determined mechanism, and that laforin, which binds tightly to the polymer, is normally present during glycogen metabolism to limit this phosphorylation
  • mutations affected the interaction between mutant laf331 and laf317, thereby suggesting that, although the mutation is specific to laf331, the functional properties of the laf331–laf317 heterodimers might have been affected
  • deletions or missense mutations in either malin or laforin not only cause loss of function of the native proteins but also could lead to toxic gain of function due to their aggregation (PMID: 20858601))