PCYT2 deficiency

Gene: PCYT2

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: Substitution, PCYT2 gene: c.4A>G, p.(Ile2Val), exon1, chromosome 9.

Breed: Saarloos Wolfdog

Medical systems: Neurologic, ocular.

Age of onset of symptoms: Early adult for ocular signs, adult for neurological signs.

A syndrome involving ocular and neurological signs in the Saarloos Wolfdog was observed and investigated.  The Saarloos Wolfdog is a Dutch dog breed originally derived by crossing a German Shepherd dog with a Siberian grey wolf.   The syndrome is characterized by retinal degeneration observed in the young adult animal followed by neurological symptoms that occur progressively in the adult animal.  Neurological symptoms included tremors, gait anomalies, hindlimb weakness, seizures and behavioral changes including aggression. Pedigree analysis suggested an autosomal recessive hereditary disease.  DNA analysis of 11 affected dogs identified a mutation in the PCYT2 gene that was homozygous in these animals.  The PCYÙT2 gene codes for an enzyme involved in lipid metabolism that is important for the cell membrane integrity, particularly for neurons and for cells of the retina.  After studying 998 Saarloos Wolfdogs, a carrier frequency of 19.1% within the breed was established.

Veterinarians and breeders of the Saarloos Wolfdog should be aware of this disease.  DNA tests should be performed to identify carrier animals so that selective breeding can be used to eliminate the disease and the mutation from the breed.

References:

OMIA link: [2728-9615]

Christen M, Oevermann A, Rupp S, et al. (2024) PCYT2 deficiency in Saarlooswolfdogs with progressive retinal, central, and peripheral neurodegeneration. Mol Genet Metab 141:S1096-7192(24)00034-9:108149.  [pm/38277988]

Contributed by: Sandrine Guay and Gabrielle St-Louis, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS)