OMIA 000626-9615 : Mannosidosis, beta in Canis lupus familiaris

In other species: cattle , goat , springbok

Possibly relevant human trait(s) and/or gene(s) (MIM number): 248510

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2019

History: This is yet another case in which a single paper (Jolly et al., 2019) provides the first description of a disease in a species, and also reports a likely causal variant for that disease in that species.

Inheritance: Jolly et al. (2019): "The variant was validated using PCR and Sanger sequencing of DNA from related and unrelated dogs. The 2 parents and 1 littermate were heterozygous for the mutation, the 2 affected dogs (case Nos. 1 and 2) were homozygous for the mutation, and 2 other dogs from the same breeder but of different parentage were homozygous wild-type . . . . An unrelated German Shepherd dog was also homozygous wild-type."

Molecular basis: Jolly et al. (2019): "Whole-genome sequencing of 2 affected dogs resulted in 2.4 to 2.5 Gbp of sequence data . . . . Filtering the variants that were in genes associated with lysosomal storage disease, considered to be deleterious using SIFT, and were heterozygous in the dam of case No. 1 and homozygous mutant in case No. 1 resulted in 1 variant, a nonsynonymous (missense) variant in the MANBA gene. The variant was a T>A transition at CFA32:24147500 (CanFam3.1) in exon 4 of the MANBA gene. The c.560T>A variant resulted in a change of amino acid from an isoleucine to an asparagine at position 187 of the 885 amino acid β-mannosidase (MANBA) protein (p.I187 N)".

Clinical features: Jolly et al. (2019): "A neurological disease was investigated in 3 German Shepherd pups from the same litter that failed to grow normally, appeared stiff, were reluctant to move, and were deaf. They developed intermittent seizures and ataxia and had proprioceptive defects."

Pathology: Jolly et al. (2019): "Histopathology showed severe vacuolation of neurons, astrocytes in nervous tissue, renal tubular epithelial cells, and macrophages in nervous tissue, spleen, and liver. Vacuoles appeared empty with no storage material stained by periodic acid–Schiff (PAS) or Sudan black stains, leading to a diagnosis of a lysosomal storage disease and in particular an oligosaccharidosis."

Breed: German Shepherd Dog.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MANBA mannosidase, beta A, lysosomal Canis lupus familiaris 32 NC_006614.3 (24167565..24052078) MANBA Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
German Shepherd Dog Beta mannosidosis MANBA missense CanFam3.1 32 g.24,147,500T>A c.560T>A p.I187N 2019 30983534

Reference


2019 Jolly, R.D., Dittmer, K.E., Garrick, D.J., Chernyavtseva, A., Hemsley, K.M., King, B., Fietz, M., Shackleton, N.M., Fairley, R., Wylie, K. :
β-Mannosidosis in German Shepherd Dogs. Vet Pathol :300985819839239, 2019. Pubmed reference: 30983534. DOI: 10.1177/0300985819839239.

Edit History


  • Created by Frank Nicholas on 24 Apr 2019
  • Changed by Frank Nicholas on 24 Apr 2019