Recurrent pulmonary inflammatory disease

Gene: AKNA

Transmission: Autosomal recessive

For an autosomal recessive genetic disease, an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease, but are carrier animals that can pass the mutation on to future generations.

Mutation: Deletion, AKNA gene; c.2717_2720 del. ACAG, p.(D906A fs STOP 173), chr.11.

Medical system: Respiratory

Breeds: Collie, Collie - Rough

Age of onset of symptoms: Within a week of birth, recurring.

Three Rough Collies from an inbred European pedigree suffered shortly after birth from respiratory infections involving nasal discharge, coughing, a rapid and shallow respiration, fever, and vomiting.  Respiratory infections responded to antibiotic treatment but were recurring.  Clinical signs were similar to those seen in cases of primary ciliary dyskinesia, however, molecular studies revealed a mutation in the AKNA gene which codes for a transcription factor involved in inflammatory immune responses.  A DNA survey of 88 Rough Collies indicated a carrier frequency of the mutation of 20.5%.  A DNA test for the mutation will help breeders of Rough Collies to eliminate this disease and eventually this mutation from their animals.

References:

OMIA link: [2205-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Hug P, Anderegg L, Kehl A, Jagannathan V, et al. (2019) AKNA frameshift variant in three dogs with recurrent inflammatory pulmonary disease. Genes (Basel) 10(8):567. [pm/31357536]

Contributed by:  Mahis Groleau-Rouleau and Louis-Philippe Hamelin, Class of 2028, Faculty of Veterinary Medicine, University of Montreal.  (Translation, DWS)