NHLRC1 dodecamer repeat expansion demonstrated by whole genome sequencing in a Chihuahua with Lafora disease

Abstract

Lafora disease is an autosomal recessive disorder that causes myoclonic epilepsy1,2,3. The disease is characterized by the presence of polyglucosan inclusion bodies (Lafora bodies), predominantly in the central nervous system. More than 90% of human Lafora disease cases are caused by genetics variants in either EPM2A, encoding the laforin glucan phosphatase or NHLRC1 encoding the NHL repeat containing E3 ubiquitin protein ligase 1, which has also been termed EPM2B or malin1,2,4 . Lafora disease in animals has similar clinical signs as the human disease, including spontaneous and reflex myoclonus, jerks and generalized tonic clonic seizures. Case description: A 10-year old female spayed Chihuahua was presented at the Small Animal Hospital of the University of Bern. Lafora disease was suspected based on neurological examination, seizures semiology, MRI and CSF findings. An EDTA blood sample was collected for further genetic analysis.