title: Mutations in NHLRC1 cause progressive myoclonus epilepsy.
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.
authors.affiliation: Program in Genetics and Genomic Biology, Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
authors.forename: Elayne M
authors.initials: EM
authors.lastname: Chan
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Young
authors.forename: Leonarda
authors.initials: L
authors.lastname: Ianzano
authors.forename: Iulia
authors.initials: I
authors.lastname: Munteanu
authors.forename: Xiaochu
authors.initials: X
authors.lastname: Zhao
authors.forename: Constantine C
authors.initials: CC
authors.lastname: Christopoulos
authors.forename: Giuliano
authors.initials: G
authors.lastname: Avanzini
authors.forename: Maurizio
authors.initials: M
authors.lastname: Elia
authors.forename: Cameron A
authors.initials: CA
authors.lastname: Ackerley
authors.forename: Nebojsa J
authors.initials: NJ
authors.lastname: Jovic
authors.forename: Saeed
authors.initials: S
authors.lastname: Bohlega
authors.forename: Eva
authors.initials: E
authors.lastname: Andermann
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
authors.forename: Antonio V
authors.initials: AV
authors.lastname: Delgado-Escueta
authors.forename: Berge A
authors.initials: BA
authors.lastname: Minassian
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
mesh_terms: D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D006720:Homozygote; D006801:Humans; D020192:Lafora Disease / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D020191:Myoclonic Epilepsies, Progressive / Q000201:enzymology / Q000235:genetics*; D010375:Pedigree; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D017384:Sequence Deletion; D044767:Ubiquitin-Protein Ligases
chemical_list: D002352:Carrier Proteins; C478960:NHLRC1 protein, human; D044767:Ubiquitin-Protein Ligases; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C114990:EPM2A protein, human