Mutations in NHLRC1 cause progressive myoclonus epilepsy.
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.
Chan
Elayne M
EM
Program in Genetics and Genomic Biology, Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
Young
Edwin J
EJ
Ianzano
Leonarda
L
Munteanu
Iulia
I
Zhao
Xiaochu
X
Christopoulos
Constantine C
CC
Avanzini
Giuliano
G
Elia
Maurizio
M
Ackerley
Cameron A
CA
Jovic
Nebojsa J
NJ
Bohlega
Saeed
S
Andermann
Eva
E
Rouleau
Guy A
GA
Delgado-Escueta
Antonio V
AV
Minassian
Berge A
BA
Scherer
Stephen W
SW
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
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