Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 271900 (trait) , 608034 (gene)

Mendelian trait/disorder: yes

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2021

Species-specific name: spongy encephalopathy

Species-specific description: A neurodegenerative syndrome in cats analogous to human Canavan disease.

Inheritance: Takaichi et al. (2021): "Four female mixed-breed cats exhibiting neurological signs consistent with intracranial disease were examined ... . These cats were bred in different regions in Japan and considered to be an unrelated pedigree."

Molecular basis: Takaichi et al. (2021) identified ASPA as a likely candidate gene based on clinical features. "A single base substitution of guanine for cytosine (c.859G>C) in exon 6 was identified in all affected cats ... . This missense mutation is predicted to result in an amino acid substitution of a conserved alanine to proline (A287P). ... The mutation showed a SIFT score of 0.00 and was predicted to be highly damaging to the functions of the ASPA protein."

Clinical features: Takaichi et al. (2021): "clinical signs were gait disturbance and head tremors appearing between 1 and 19 months of age. Dysstasia, intension tremors, and seizures were present in the terminal stages, and the median age of death was 11 months ... . In MRI analyses, hypointense lesions on T1-weighted (T1W) images and hyperintense lesions on T2W images were detected in the cerebral cortex, hippocampus, cerebellum, and brain stem ... . The GC-MS [gas chromatography–mass spectrometry] analysis identified the aberrant excretion of NAA [N-acetylaspartate] in the urine" of one affected cat.

Pathology: Takaichi et al. (2021): "Postmortem analysis revealed vacuolar changes predominantly distributed in the gray matter of the cerebrum and brain stem as well as in the cerebellar Purkinje cell layer. Immunohistochemically, these vacuoles were surrounded by neurofilaments and sometimes contained MBP- and Olig2-positive cells. Ultrastructurally, a large number of intracytoplasmic vacuoles containing mitochondria and electron-dense granules were detected in the cerebral cortex."

Associated gene: