Granuloprival cerebellar cortical degeneration in a mixed breed dog with an EMC1 mutation

A mixed-breed male puppy had a 6-month history of progressive cerebellar ataxia and head tremors without a clinically detectable cause. Euthanasia with a necropsy was elected based on the severity of the puppy's clinical signs and lack of response to treatment. At necropsy, the cerebellum was mildly atrophied, and microscopically there was severe diffuse loss of the cerebellar internal granular cell layer with minimal loss of Purkinje cells (granuloprival degeneration). A novel, heterozygous point mutation in the endoplasmic reticulum membrane protein complex subunit 1 (EMC1) gene was detected via whole genome sequencing. Homozygous and heterozygous EMC1 variants are associated with neurodevelopmental delay and cerebellar atrophy in humans. This is the first report of a canine EMC1 mutation with association to granuloprival cerebellar degeneration and expands the genetic implications of this uncommon phenotype of cerebellar atrophy.