OMIA:000625-9615 : Mannosidosis, alpha in Canis lupus familiaris (dog)
Categories: Lysosomal storage disease
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Probably autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2023
Cross-species summary: A lysosomal storage disease in which there is a buildup (storage) of mannose-rich compounds, due to the lack of the enzyme alpha-mannosidase, whose task is to cleave mannose from such compounds. Clinical signs include ataxia, head tremor, aggression, and finally paralysis and death.
Molecular basis: Bullock et al. (2023): "A whole genome sequence generated with DNA from the affected [Doberman Pinscher] dog contained a likely causal, homozygous missense variant in MAN2B1 that predicted an Asp104Gly amino acid substitution that was unique among whole genome sequences from over 4000 dogs. A lack of detectable α-mannosidase enzyme activity confirmed a diagnosis of a-mannosidosis."
Clinical features: Bullock et al. (2023): A "7-month-old Doberman Pinscher dog presented with progressive neurological signs and brain atrophy suggestive of a hereditary neurodegenerative disorder. The dog was euthanized due to the progression of disease signs."
Pathology: Bullock et al. (2023): "Microscopic examination of tissues [from the affected Doberman Pinscher] ... revealed massive accumulations of vacuolar inclusions in cells throughout the central nervous system, suggestive of a lysosomal storage disorder. ... In addition to the vacuolar inclusions characteristic of α-mannosidosis, the dog exhibited accumulations of autofluorescent intracellular inclusions in some of the same tissues. The autofluorescence was similar to that which occurs in a group of lysosomal storage disorders called neuronal ceroid lipofuscinoses (NCLs). As in many of the NCLs, some of the storage bodies immunostained strongly for mitochondrial ATP synthase subunit c protein. This protein is not a substrate for α-mannosidase, so its accumulation and the development of storage body autofluorescence were likely due to a generalized impairment of lysosomal function secondary to the accumulation of α-mannosidase substrates. ... In addition to storage body accumulation, glial activation indicative of neuroinflammation was observed in the brain and spinal cord of the proband."
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|MAN2B1||mannosidase, alpha, class 2B, member 1||Canis lupus familiaris||20||NC_051824.1 (49964867..49980270)||MAN2B1||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1628||Doberman Pinscher||Mannosidosis, alpha||MAN2B1||missense||Naturally occurring variant||Dog10K_Boxer_Tasha||20||g.49320989A>G||c.311A>G||p.(D104G)||XM_005632833.4; XP_005632890.1||2023||37761886|
Cite this entry
|2023||Bullock, G., Johnson, G.S., Pattridge, S.G., Mhlanga-Mutangadura, T., Guo, J., Cook, J., Campbell, R.S., Vite, C.H., Katz, M.L. :|
|A homozygous MAN2B1 missense mutation in a Doberman Pinscher dog with neurodegeneration, cytoplasmic vacuoles, autofluorescent storage granules, and an α-mannosidase deficiency. Genes (Basel) 14:, 2023. Pubmed reference: 37761886 . DOI: 10.3390/genes14091746.|
- Created by Imke Tammen2 on 02 Oct 2023
- Changed by Imke Tammen2 on 02 Oct 2023