Mutations in NHLRC1 cause progressive myoclonus epilepsy

Nat Genet. 2003 Oct;35(2):125-7. doi: 10.1038/ng1238. Epub 2003 Sep 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Carrier Proteins / genetics*
  • Cohort Studies
  • Female
  • Homozygote
  • Humans
  • Lafora Disease / genetics
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Myoclonic Epilepsies, Progressive / enzymology
  • Myoclonic Epilepsies, Progressive / genetics*
  • Pedigree
  • Protein Tyrosine Phosphatases / genetics*
  • Protein Tyrosine Phosphatases, Non-Receptor
  • Sequence Deletion

Substances

  • Carrier Proteins
  • NHLRC1 protein, human
  • Protein Tyrosine Phosphatases
  • Protein Tyrosine Phosphatases, Non-Receptor
  • EPM2A protein, human

Associated data

  • GENBANK/AF084535
  • GENBANK/AY324850
  • GENBANK/BK001499
  • GENBANK/BK001510
  • GENBANK/BK001524
  • OMIM/254780
  • RefSeq/NM_014805
  • RefSeq/NM_175340