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

ABSTRACT

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.