OMIA 001406-9615 : Pyruvate dehydrogenase deficiency in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 608782

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2007

Cross-species summary: PDH deficiency.

Species-specific description: Deficiency in pyruvate dehydrogenase phosphatase 1 in Clumber and Sussex Spaniels is characterized by exercise intolerance, lactic acidosis, and collapse after exercise. The causative mutation is the same in these breeds.

Edited by Vicki N. Meyers-Wallen, VMD, PhD, Dipl. ACT

Mapping: CFA (29)

Molecular basis: Cameron et al. (2007): c.754C>T; p.Q252* in Clumber spaniels and Sussex spaniels

Clinical features: Affected dogs show exercise intolerance, lactic acidosis, and post-exercise collapse.

Management includes exercise restriction and a high-fat diet with thiamine and carnitine supplementation (Cameron et al., 2007).

Pathology: PDP1 is a key component of the pyruvate dehydrogenase complex (PDHC) that controls the rate of tricarboxylic acid entry into the citric acid cycle. During exercise, large quantities of lactate and pyruvate are generated through the anaerobic pathway. PDP1 deficiency causes severe reduction in pyruvate entry into the citric acid cycle, leading to insufficient generation of ATP and lactate and pyruvate acidosis when muscle is exercised (Cameron et al., 2007).

Prevalence: Of 100 Clumber Spaniels tested, 20 were carriers and 1 was homozygous for the mutation. There is thought to be a high frequency of heterozygotes amongst Clumber Spaniels, but fewer affected dogs alive than expected. This suggests that affected dogs may be at risk for prenatal or neonatal mortality (Cameron et al., 2007).

Control: Since the Clumber and Sussex Spaniel gene pools are small in the USA, gradual elimination of the mutation can be achieved by testing all dogs prior to breeding, and to breeding carriers only to noncarriers. Breeding of affected dogs should be avoided.

Genetic testing: There is a test available to identify carrier and affected dogs.

Breeds: Clumber Spaniel, Sussex Spaniel.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
PDP1 pyruvate dehyrogenase phosphatase catalytic subunit 1 Canis lupus familiaris 29 NC_006611.3 (38783945..38792141) PDP1 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
Clumber Spaniel Sussex Spaniel Pyruvate dehydrogenase deficiency PDP1 nonsense (stop-gain) c.754C>T p.Q252* 2007 17095275

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.
2007 Cameron, JM., Maj, MC., Levandovskiy, V., MacKay, N., Shelton, GD., Robinson, BH. :
Identification of a canine model of pyruvate dehydrogenase phosphatase 1 deficiency. Mol Genet Metab 90:15-23, 2007. Pubmed reference: 17095275. DOI: 10.1016/j.ymgme.2006.09.011.
2004 Abramson, CJ., Platt, SR., Shelton, GD. :
Pyruvate dehydrogenase deficiency in a Sussex spaniel. J Small Anim Pract 45:162-5, 2004. Pubmed reference: 15049576.
2000 Shelton, G.D., Van Ham, L., Bhatti, S., Cook-Olson, S., Johnson, K., Barshop, B., Toone, J., Applegarth, D. :
Pyruvate dehydrogenase deficiency in Clumber and Sussex spaniels in the United States and Belgium J. Vet. Intern. Med. 14:342 only, 2000.
1980 Houlton, JE., Herrtage, ME. :
Mitochondrial myopathy in the Sussex spaniel. Vet Rec 106:206, 1980. Pubmed reference: 7361423.
1979 Griffiths, IR., Duncan, ID. :
Collapsing Clumber spaniels. Vet Rec 105:405, 1979. Pubmed reference: 552740.
Herrtage, M.E., Houlton, J.E.F. :
Collapsing Clumber Spaniels Veterinary Record 105:334, 1979. Pubmed reference: 516334.

Edit History


  • Created by Frank Nicholas on 21 Jul 2011
  • Changed by Martha MaloneyHuss on 08 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 28 Aug 2016