OMIA 000402-9940 : Gangliosidosis, GM1 in Ovis aries

In other species: domestic cat , cattle , dog , emu

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 230500 , 230650

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2012

Cross-species summary: A lysosomal storage disease in which there is a buildup (storage) of GM1 gangliosides (a type of glycolipid) in various tissues, due to the lack of the enzyme beta-galactosidase, whose task is to break down the GM1 ganglioside into its constituents. Characterised by progressive neuromuscular dysfunction and impaired growth from an early age.

Molecular basis: A Genome-Wide Association Study (GWAS) for this disorder led Walker et al. (2012) to a region on chromosome OAR19 which is homologous to the region of human chromosome HSA3 that includes the candidate gene for this disorder, namely GLB1 which encodes β-galactosidase. Subsequent sequencing of the candidate gene by the same authors identified "a G to T base pair substitution mutation in exon 6 of ovine GLB1 causing a cysteine to phenylalanine amino acid substitution".

Ahern-Rindell (2018) reported what could be the same variant: "A missence mutation has been found in exon 6 of the affected sheep’s beta-gal gene resulting in the loss of a cysteine residue possibly leading to the synthesis of an altered structural beta-gal but with detectable levels of protein product confirmed by Western Blotting."

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
GLB1 galactosidase beta 1 Ovis aries 19 NC_040270.1 (8040366..7939562) GLB1 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
Romney Marsh Gangliosidosis, GM1 GLB1 missense c.G>T p.CxxxF 2012 Reference not in PubMed; see OMIA 000402-9940 for reference details

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2018 Ahern-Rindell, A. :
A variant of GM1 gangliosidosis in a sheep model Molecular Genetics and Metabolism 123:S17, 2018.
2012 Walker, K.M., Holler, L.D., Beever, J.E. :
Ovine GM1-gangliosidosis is caused by a mutation in GLB1 Plant & Animal Genome (PAG) XX :Abstract P0589, 2012.
2001 Ryder, S.J., Simmons, M.M. :
A lysosomal storage disease of Romney sheep that resembles human type 3 G(M1) gangliosidosis Acta Neuropathologica 101:225-228, 2001. Pubmed reference: 11307621.
1995 Skelly, B.J., Jeffrey, M., Franklin, R.J.M., Winchester, B.G. :
A new form of ovine G(M1)-gangliosidosis Acta Neuropathologica 89:374-379, 1995. Pubmed reference: 7610770.
1994 Murnane, R.D., Prieur, D.J., Ahernrindell, A.J., Holler, L.D., Parish, S.M. :
Clinical and Clinicopathologic Characteristics of Ovine GM-1 Gangliosidosis Journal of Veterinary Internal Medicine 8:221-223, 1994. Pubmed reference: 8064659.
1991 Murnane, R.D., Ahern-Rindell, A.J., Prieur, D.J. :
Ultrastructural lesions of ovine GM1 gangliosidosis. Mod Pathol 4:755-62, 1991. Pubmed reference: 1788267.
Murnane, R.D., Ahern-Rindell, A.J., Prieur, D.J. :
Ovine GM1 Gangliosidosis Small Ruminant Research 6:109-118, 1991.
Murnane, R.D., Hartley, W.J., Prieur, D.J. :
Similarity of Lectin Histochemistry of a Lysosomal Storage Disease in a New-Zealand Lamb to That of Ovine GM1 Gangliosidosis Veterinary Pathology 28:332-335, 1991. Pubmed reference: 1949511.
Murnane, R.D., Wright, R.W., Ahern-Rindell, A.J., Prieur, D.J. :
Animal Model - Prenatal Lesions in an Ovine Fetus with GM1 Gangliosidosis American Journal of Medical Genetics 39:106-111, 1991. Pubmed reference: 1907804. DOI: 10.1002/ajmg.1320390123.
Prieur, D.J., Ahern-Rindell, A.J., Murnane, R.D. :
Ovine GM-1 Gangliosidosis American Journal of Pathology 139:1511-1513, 1991. Pubmed reference: 1750516.
1990 Prieur, D.J., Ahern-Rindell, A.J., Murnane, R.D., Wright, R.W., Parish, S.M. :
Inheritance of an Ovine Lysosomal Storage Disease Associated with Deficiencies of Beta-Galactosidase and Alpha- Neuraminidase Journal of Heredity 81:245-249, 1990. Pubmed reference: 2125614.
1989 Ahern-Rindell, A.J., Murnane, R.D., Prieur, D.J. :
Interspecific Genetic Complementation Analysis of Human and Sheep Fibroblasts with Beta-Galactosidase Deficiency Somatic Cell and Molecular Genetics 15:525-533, 1989. Pubmed reference: 2512653.
Prieur, D.J., Ahern-Rindell, A.J. :
Interspecific complementation analysis evidence that the lysosomal storage disease of sheep with deficiencies of beta-galactosidase and alpha-neuraminidase is due to a mutation of the beta-galactosidase structural gene (Abstract) American Journal of Human Genetics 45 (suppl.):A213 only, 1989.
1988 Ahern-Rindell, A.J., Prieur, D.J., Murnane, R.D., Raghaven, S.S., Daniel, P.F., McCluer, R.H., Walkley, S.U., Parish, S.M. :
Inherited lysosomal storage disease associated with deficiencies of beta-galactosidase and alpha-neuraminidase in sheep American Journal of Medical Genetics 31:39-56, 1988. Pubmed reference: 3146925. DOI: 10.1002/ajmg.1320310108.
1986 Ahern-Rindell, A.J., Prieur, D.J., Murnane, R.D. :
An inherited lysosomal storage disease of sheep associated with deficiencies of beta-galactosidase and alpha-neuraminidase (Abstract) American Journal of Human Genetics 39:A3 only, 1986.

Edit History


  • Created by Frank Nicholas on 06 Sep 2005
  • Changed by Frank Nicholas on 19 Jan 2012
  • Changed by Frank Nicholas on 21 Mar 2012
  • Changed by Frank Nicholas on 08 Feb 2018