Cerebellar ataxia is clinically and genetically heterogeneous, and candidate variant prioritization is particularly difficult when only a single affected animal is available. We combined structural MRI of one affected Border Collie and six controls with whole-genome sequencing of the affected dog and 31 comparison dogs. MRI revealed widened cerebellar folial spaces and reduced bilateral cerebellar gray matter volume, without global brain atrophy or spinal cord lesioning. Parallel heterozygous and recessive variant screens, together with identity-by-descent, runs-of-homozygosity, structural-variant, and repeat-expansion analyses, narrowed the candidates to six non-MODIFIER variants. Among these, a heterozygous PACSIN1 splice-donor variant (chr12:3,985,222 T > G) was private to the affected dog in the analyzed cohort and affects a conserved residue in the F-BAR domain. No segregation, replication, or functional validation data are currently available. These results prioritize the PACSIN1 variant as a testable candidate and demonstrate the utility of imaging-guided genomic prioritization in underpowered veterinary cohorts.
Jin et al. (Sat,) studied this question.