In other species: dog , taurine cattle , goat , springbok

Categories: Lysosomal storage disease

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 248510 (trait) , 609489 (gene)

Mendelian trait/disorder: yes

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2024

Molecular basis: Katz et al. (2024): "Whole genome sequence analysis [of a single affected cat] identified a homozygous missense variant c.2506G>A in MANBA that predicts a p.Gly836Arg alteration in the encoded lysosomal enzyme β -mannosidase. This variant was not present in the whole genome or whole exome sequences of any of the 424 cats represented in the 99 Lives Cat Genome dataset. ... The MANBA variant in the proband was associated with a complete absence of detectable β–mannosidase enzyme activity in the cerebellar cortex and cerebral cortex ... . "

Clinical features: Katz et al. (2024): "A 6-month-old spayed female cat of unknown ancestry ... exhibited apparent retinal degeneration based on a fundus appearance suggestive of chorioretinitis. Muscle tone was normal and symmetric. Upon neurological examination the cat was found to have dull mentation, a tetraparetic gait, and delayed conscious proprioception in all four limbs ... . Due to the progression of disease signs, the cat was humanely euthanized at approximately 10.5 months of age."

Pathology: Katz et al. (2024): "Postmortem examination of brain and retinal tissues revealed massive accumulations of vacuolar inclusions in most cells, similar to those reported in animals of other species with hereditary β -mannosidosis. ... In addition to the vacuolar inclusions, some cells in the brain of the affected cat contained inclusions that exhibited lipofuscin-like autofluorescence."

Breed: Domestic Shorthair.
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: