title: Expanded repeat in canine epilepsy.
abstract: Epilepsy afflicts 1% of humans and 5% of dogs. We report a canine epilepsy mutation and evidence for the existence of repeat-expansion disease outside humans. A canid-specific unstable dodecamer repeat in the Epm2b (Nhlrc1) gene recurrently expands, causing a fatal epilepsy and contributing to the high incidence of canine epilepsy. Tracing the repeat origins revealed two successive events, starting 50 million years ago, unique to canid evolution. A genetic test, presented here, will allow carrier and presymptomatic diagnosis and disease eradication. Clinicopathologic characterization establishes affected animals as a model for Lafora disease, the most severe teenage-onset human epilepsy.
authors.affiliation: The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
authors.forename: Hannes
authors.initials: H
authors.lastname: Lohi
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Young
authors.forename: Susan N
authors.initials: SN
authors.lastname: Fitzmaurice
authors.forename: Clare
authors.initials: C
authors.lastname: Rusbridge
authors.forename: Elayne M
authors.initials: EM
authors.lastname: Chan
authors.forename: Mike
authors.initials: M
authors.lastname: Vervoort
authors.forename: Julie
authors.initials: J
authors.lastname: Turnbull
authors.forename: Xiao-Chu
authors.initials: XC
authors.lastname: Zhao
authors.forename: Leonarda
authors.initials: L
authors.lastname: Ianzano
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Paterson
authors.forename: Nathan B
authors.initials: NB
authors.lastname: Sutter
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Ostrander
authors.forename: Catherine
authors.initials: C
authors.lastname: André
authors.forename: G Diane
authors.initials: GD
authors.lastname: Shelton
authors.forename: Cameron A
authors.initials: CA
authors.lastname: Ackerley
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
authors.forename: Berge A
authors.initials: BA
authors.lastname: Minassian
mesh_terms: D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D042622:DNA Repeat Expansion; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs / Q000235:genetics*; D005260:Female; D020192:Lafora Disease / Q000235:genetics / Q000662:veterinary*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D012333:RNA, Messenger