OMIA 001406-9615 : Pyruvate dehydrogenase deficiency in Canis lupus familiaris
Edited by Vicki N. Meyers-Wallen, VMD, PhD, Dipl. ACTMapping: 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|
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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.
|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|
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.|
- 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