Pycnodysostose

Gene: CTSK

Transmission: Autosomal, likely 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: Substitution (nonsense), CTSK gene; c.724 C>T, p.(Arg242STOP), exon6, chromosome A1.

Breed: Domestic Cat

Medical system: Skeletal, lysosomal storage disease

Age of onset of symptoms: From birth or during growth phase.

In humans, pycnodysostosis (PD) is a rare genetic disorder affecting bone development. The phenotype associated with PD includes short stature, short limbs, an atypical facial appearance, and dense but fragile bones (osteopetrosis).  PD is caused by mutations within the CTSK gene, which codes for the cathepsin K protein, a lysosomal cysteine protease found in lysosomes.  Cathepsin K is important for the bone remodeling function of osteoclasts, and disruption of the CTSK gene accounts for the osteopetrosis phenotype seen in PD. It is believed that the French painter Toulouse-Letrec was afflicted by PD.

A single domestic cat was presented with poor growth, facial anomalies, musculoskeletal pain and pathological fractures, and a diagnosis of PD was made.  DNA analysis revealed a homozygous premature stop mutation within the CTSK gene that would account for the observed phenotype.  No pedigree analysis could be performed, and analysis of 195 additional cats failed to detect the mutation within the larger feline population.  At present, the described mutation in the CTSK gene is of academic interest but is not of clinical concern to veterinarians or to cat breeders.

References:

OMIA link: [2607-9685]

Lyraki M, Hibbert A, Langley-Hobbs S, et al. (2022) CTSK variant implicated in suspected pyknodysostosis in a domestic cat. JFMS Open Rep 8:20551169221137536.  [pm/36532681]

Contributed by: Henry Nguyen and Audigan Vaslier, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS)