A Novel Frameshift Variant in SPAG1 Likely Causes Primary Ciliary Dyskinesia in Cocker Spaniels in Australia

Primary ciliary dyskinesia (PCD) is a clinical syndrome that in dogs primarily manifests as chronic respiratory disease associated with cilial malfunction. The current study employs whole-genome sequencing and a candidate gene approach to uncover the genetic basis of PCD in three Cocker Spaniel siblings following diagnosis of their respiratory cilia by scanning electron microscopy and high-speed video microscopy. Absence of the disorder in the parents suggested autosomal recessive inheritance. A 29 bp frameshift insertion in the eleventh exon of the candidate gene sperm-associated antigen 1 (SPAG1) [NC_049234.1:g.2213788_2213789insGGCGGCGGCAAGCGGCCGGAGAGGGGCGC] was identified as likely causative for PCD in this family. The 29 bp frameshift variant was unobserved in a public variant call file including 1987 dogs from the Dog10K resource however an in-frame insertion was sometimes observed at the same locus. A Cocker Spaniel with similar symptoms from a different family tested negative for the identified variant suggesting that there are multiple causes for the condition in Cocker Spaniels.