Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 102771 (gene) , 615809 (trait)

Links to relevant human diseases in MONDO:

• MONDO:0014351: pontocerebellar hypoplasia type 9

Mendelian trait/disorder: yes

Mode of inheritance: Probably autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2024

Species-specific name: Cirneco oculo-neurological syndrome

Species-specific symbol: CONS

Molecular basis: Murgiano et al. (2024) "undertook homozygosity mapping and whole-genome sequencing ... [and] detected a 1-bp deletion in chromosome 6 [in affected Cirneco dell′ Etna dogs] that was predicted to cause a frameshift and premature stop codon within the canine AMPD2 gene, which encodes adenosine monophosphate deaminase, an enzyme that converts adenosine 5′-monophosphate (AMP) to inosine 5’-monophosphate (IMP). Genotyping of the available Cirneco population suggested perfect segregation between cases and controls for the variant. Moreover, this variant was absent in canine genomic databases comprised of thousands of unaffected dogs." The authors acknowledge that the low number of cases and of genotyped controls of this rare breed is a limitation of this study. 

Clinical features: Murgiano et al. (2024) reported two Cirneco dell′ Etna dogs from the same litter with retinal degeneration, along with tremors, gait alteration and signs described as either atypical seizures or paroxysmal dyskinesias.
"Analysis of the brain MRI ... showed a discrete area of bilaterally symmetric, peri-ventricular T2 hyperintensity ... . This signal abnormality extended towards the internal capsule, where it was accompanied by increased T2 signal within the caudate nuclei bilaterally (right greater than left). There was also moderate ventriculomegaly involving the lateral ventricles. This appeared to result from diffuse thinning of cerebral white matter, most notable in the ventral temporal lobe. The results of the CSF analysis were within normal ranges... . The MRI of the cervical spine did not reveal any abnormalities."

Breed: Cirneco dell'Etna (Dog) (VBO_0200365).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: