Pontocerebellar hypoplasia, AMPD2-linked

Gene: AMPD2

Transmission: Autosomal, recessive (likely)

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, AMPD2 gene; c.2131delG, p.(Asp711Met frameshift STOP 12), exon15, chromosome 6.

Breed: Cirneco dell’Etna

Medical system: Neurologic, ocular.

Age of onset of symptoms: 2 years for tremors, 4 years for retinal degeneration.

The Cirneco dell’Etna dog breed is a rare breed of sighthound originating from Sicily.  Two adult dogs within a litter displayed a syndrome of oculo-neurological clinical signs, including retinal degeneration, head tremors and seizure-like episodes.  Nuclear magnetic resonance imaging of the brain showed increased cerebral ventricular size and thinning of white matter was observed.  DNA studies revealed a homozygous mutation in the AMPD2 gene; this gene codes for an enzyme involved in energy homeostasis known to be important for retinal and brain function. Limited pedigree analysis showed that the single grandmother of the two clinical cases was a carrier for the mutation.  A survey of 33 normal Cirneco dell’Etnadogs resulted in a carrier frequency rate of 9.1%.  The mutation was not found in 1204 dogs of other breeds.

Veterinarians and breeders of Cirneco dell’Etna dogs should be aware of this disease.  DNA testing should be performed in order to identify carriers of the mutation so that selective breeding can be performed to eliminate the disease and the mutation from the breed.

References:

OMIA link: [2838-9615]

Murgiano L, Niggel JK, Benedicenti L, (2024) Frameshift variant in AMPD2 in Cirneco dell’Etna dogs with retinopathy and tremors. Genes (Basel) 15:238.  [pm/38397227]

Contributed by: Benjamin Rousseau and Justin Côté, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS)