Expanded repeat in canine epilepsy.
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.
Lohi
Hannes
H
The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
Young
Edwin J
EJ
Fitzmaurice
Susan N
SN
Rusbridge
Clare
C
Chan
Elayne M
EM
Vervoort
Mike
M
Turnbull
Julie
J
Zhao
Xiao-Chu
XC
Ianzano
Leonarda
L
Paterson
Andrew D
AD
Sutter
Nathan B
NB
Ostrander
Elaine A
EA
André
Catherine
C
Shelton
G Diane
GD
Ackerley
Cameron A
CA
Scherer
Stephen W
SW
Minassian
Berge A
BA
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
D012333:RNA, Messenger