Lafora Disease: Molecular Etiology

ÇAĞLAYAN S. H.

EPILEPSI, vol.24, no.1, pp.1-7, 2018 (ESCI) identifier

  • Publication Type: Article / Review
  • Volume: 24 Issue: 1
  • Publication Date: 2018
  • Doi Number: 10.14744/epilepsi.2017.48278
  • Journal Name: EPILEPSI
  • Journal Indexes: Emerging Sources Citation Index (ESCI), TR DİZİN (ULAKBİM)
  • Page Numbers: pp.1-7
  • Keywords: EPM2A and NHLRC1 gene mutations, genotype-phenotype relationship, Lafora progressive myoclonus epilepsy, LD pathogenesis, PROGRESSIVE MYOCLONUS EPILEPSY, GENOTYPE-PHENOTYPE CORRELATIONS, EPM2A GENE, GLYCOGEN ACCUMULATION, MUTATIONS, AUTOPHAGY, BODIES, ONSET, MALIN, NEURODEGENERATION
  • Dokuz Eylül University Affiliated: No

Abstract

Lafora Disease (LD) is a fatal neurodegenerative condition characterized by the accumulation of abnormal glycogen inclusions known as Lafora bodies (LBs). Patients with LD manifest myoclonus and tonic-clonic seizures, visual hallucinations, and progressive neurological deterioration beginning at the age of 8-18 years. Mutations in either EPM2A gene encoding protein phosphatase laforin or NHLRC1 gene encoding ubiquitin-ligase malin cause LD. Approximately, 200 distinct mutations accounting for the disease are listed in the Lafora progressive myoclonus epilepsy mutation and polymorphism database. In this review, the genotype-phenotype correlations, the genetic diagnosis of LD, the downregulation of glycogen metabolism as the main cause of LD pathogenesis and the regulation of glycogen synthesis as a key target for the treatment of LD are discussed.