Hereditary sensory and autonomic neuropathy in a family of mixed breed dogs is associated with a novel FAM134B (RETREG1) mutation

Background: Hereditary sensory and autonomic neuropathies (HSANs) are a group of genetic disorders affecting the peripheral nervous system. Two different causative mutations have been identified in dogs: one in Border Collies and one in Spaniels and Pointers.Objectives: Clinical and genetic characterization of a HSAN in a family of mixed breed dogs.Animals: Five 7-month old mixed breed dogs from 2 related litters were presented for a 2-month history of acral mutilation and progressive pelvic limb gait abnormalities. Methods: Complete physical, neurological, electrodiagnostic, and histopathological evaluations were performed. Whole genome sequencing of 2 affected dogs (one from each litter) was used to identify variants that were homozygous in both and wild type in 184 control genomes of 94 breeds. Immunohistochemistry was used to assess protein expression. Results: Complete physical, neurological, electrodiagnostics and histological evaluations confirmed a disorder affecting sensory and autonomic nerves. Whole genome sequencing identified a missense single nucleotide polymorphism in the FAM134B (RETREG1) gene (c.656C>T, p.P219L). All affected dogs were homozygous for the mutation, which was not detected in 1142 dogs from different breeds. Immunohistochemistry showed no expression of FAM134B in the cerebellum of affected dogs. One of the affected dogs lived for 5 years and showed slow and gradual progression of the clinical signs.