OMIA:001371-9615 : L-2-hydroxyglutaricacidemia in Canis lupus familiaris (dog)

In other species: domestic cat

Categories: Nervous system phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 236792 (trait) , 609584 (gene)

Links to MONDO diseases:

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2007

Species-specific name: L-2-hydroxyglutaric aciduria

Species-specific symbol: L-2-HGA

Species-specific description: The first cases of this inborn error of metabolism in animals were reported by Abramson et al. (2001, 2003) [FN: 7 Oct 2003]

Molecular basis: Using a candidate gene strategy (based on the homologous disorder in humans), Penderis et al. (2007) sequenced "all 10 canine L2HGDH exons (with flanking intron regions) from the [Staffordshire bull terrier] affected dogs and two carrier dogs" and identified a causal mutation as "two single‐nucleotide substitutions separated by a single invariant T nucleotide in exon 10 (c[1297T→C; 1299c→t]; p[Leu433Pro; His434Tyr])". Sanchez-Masian et al. (2012) identified a different mutation in the same gene in a family of Yorkshire Terriers: a base substitution "at the translation initiation codon of the homolog canine L2HGDH gene was detected (c.1A>G; p.Met1?)". Farias et al. (2012) reported the same mutation in the same breed.

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Breeds: Staffordshire Bull Terrier (Dog) (VBO_0201296), West Highland White Terrier (Dog) (VBO_0201415), Yorkshire Terrier (Dog) (VBO_0201448).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
L2HGDH L-2-hydroxyglutarate dehydrogenase Canis lupus familiaris 8 NC_051812.1 (26937999..26899306) L2HGDH 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.

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
735 Staffordshire Bull Terrier (Dog) L-2-hydroxyglutaricacidemia L2HGDH delins, small (<=20) Naturally occurring variant CanFam3.1 8 g.26723470_26723472delinsAAG c.1298_1300delinsCTT p.(L433_H434delinsPY) XM_858437.5; XP_863530.2; published as ENSCAFG00000014237; CanFam1.0: (c[1297T→C; 1299c→t]; p[Leu433Pro; His434Tyr]; coordinates in the table have been updated to a recent reference genome and / or transcript 2007 17475916
427 Yorkshire Terrier (Dog) L-2-hydroxyglutaricacidemia L2HGDH missense Naturally occurring variant CanFam3.1 8 g.26760351T>C c.1A>G p.(M1?) XM_858437.5; published as p.(Met1?) 2012 22843824 Genomic coordinates in CanFam3.1 provided by Robert Kuhn

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2012). OMIA:001371-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

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.

2016 Shea, A., De Risio, L., Carruthers, H., Ekiri, A., Beltran, E. :
Clinical features and disease progression of L-2-hydroxyglutaric aciduria in 27 Staffordshire bull terriers. Vet Rec , 2016. Pubmed reference: 27729589. DOI: 10.1136/vr.103783.
2014 Böhm, M., Henderson, H., Van der Zwan, H., Basson, S. :
L-2 hydroxyglutaric aciduria in a South African Staffordshire Bull Terrier. J S Afr Vet Assoc 85:1042, 2014. Pubmed reference: 24830757.
2012 Farias, F.H., Zeng, R., Johnson, G.S., Shelton, G.D., Paquette, D., O'Brien, D.P. :
A L2HGDH initiator methionine codon mutation in a Yorkshire terrier with L-2-hydroxyglutaric aciduria. BMC Vet Res 8:124, 2012. Pubmed reference: 22834903. DOI: 10.1186/1746-6148-8-124.
Sanchez-Masian, D.F., Artuch, R., Mascort, J., Jakobs, C., Salomons, G., Zamora, A., Casado, M., Fernandez, M., Recio, A., Lujan, A. :
L-2-hydroxyglutaric aciduria in two female Yorkshire terriers. J Am Anim Hosp Assoc 48:366-71, 2012. Pubmed reference: 22843824. DOI: 10.5326/JAAHA-MS-5967.
2010 Short, AD., Mellersh, CS., Platt, H., Carter, SD., Timofte, D., Lohi, H., Ollier, WE. :
Exonic mutations in the L2HGDH gene in Staffordshire bull terriers. Vet Rec 167:455-7, 2010. Pubmed reference: 20852250. DOI: 10.1136/vr.c4476.
2008 Scurrell, E., Davies, E., Baines, E., Cherubini, G.B., Platt, S., Blakemore, W., Williams, A., Schöniger, S. :
Neuropathological findings in a Staffordshire bull terrier with l-2-hydroxyglutaric aciduria. J Comp Pathol 138:160-4, 2008. Pubmed reference: 18295785. DOI: 10.1016/j.jcpa.2007.11.005.
2007 Penderis, J., Calvin, J., Abramson, C., Jakobs, C., Pettitt, L., Binns, M.M., Verhoeven, N.M., O'Driscoll, E., Platt, S.R., Mellersh, C.S. :
L-2-hydroxyglutaric aciduria: characterisation of the molecular defect in a spontaneous canine model. J Med Genet 44:334-40, 2007. Pubmed reference: 17475916. DOI: 10.1136/jmg.2006.042507.
2005 Garosi, LS., Penderis, J., McConnell, JF., Jakobs, C. :
L-2-hydroxyglutaric aciduria in a West Highland white terrier. Vet Rec 156:145-7, 2005. Pubmed reference: 15715007.
2003 Abramson, C., Platt, S., Garosi, L., Penderis, J. :
L-2-hydroxyglutaric aciduria in Staffordshire bull terriers Veterinary Record 153:95-6, 2003. Pubmed reference: 12892272.
Abramson, C.J., Platt, S.R., Jakobs, C., Verhoeven, N.M., Dennis, R., Garosi, L., Shelton, G.D. :
L-2-Hydroxyglutaric aciduria in Staffordshire Bull Terriers Journal of Veterinary Internal Medicine 17:551-6, 2003. Pubmed reference: 12892307.
2001 Abramson, C., Garosi, L., Platt, S., Penderis, J. :
Metabolic defect in Staffordshire bull terriers Veterinary Record 149:532, 2001. Pubmed reference: 11708646.

Edit History


  • Created by Frank Nicholas on 06 Nov 2010
  • Changed by Frank Nicholas on 28 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
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  • Changed by Frank Nicholas on 19 Dec 2012