Next Article in Journal
Evolutionary History of the Risk of SNPs for Diffuse-Type Gastric Cancer in the Japanese Population
Next Article in Special Issue
A Missense Variant in ALDH5A1 Associated with Canine Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD) in the Saluki Dog
Previous Article in Journal
PRPH2-Related Retinal Diseases: Broadening the Clinical Spectrum and Describing a New Mutation
Previous Article in Special Issue
A Deletion in GDF7 is Associated with a Heritable Forebrain Commissural Malformation Concurrent with Ventriculomegaly and Interhemispheric Cysts in Cats
Open AccessArticle

Mitochondrial PCK2 Missense Variant in Shetland Sheepdogs with Paroxysmal Exercise-Induced Dyskinesia (PED)

1
Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover Foundation, 30559 Hannover, Germany
2
Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland
3
Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands
4
Department of Pediatrics, Hannover Medical School, 30625 Hannover, Germany
5
Section of Clinical and Comparative Neuropathology, Institute of Veterinary Pathology at the Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität, 80539 Munich, Germany
6
Biocontrol, Labor für Veterinärmedizinische Diagnostik, 55218 Ingelheim, Germany
7
AniCura Tierklinik Trier GbR, 54294 Trier, Germany
8
Tierklinik Stommeln, 50259 Puhlheim, Germany
9
Nutritional Physiology and Animal Nutrition, University of Rostock, 18059 Rostock, Germany
10
Section of Neurology, Clinic of Small Animal Medicine, Ludwig-Maximilians-Universität, 80539 Munich, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Genes 2020, 11(7), 774; https://doi.org/10.3390/genes11070774
Received: 9 June 2020 / Revised: 7 July 2020 / Accepted: 8 July 2020 / Published: 9 July 2020
(This article belongs to the Special Issue Molecular Basis of Inherited Diseases in Companion Animals)
Four female Shetland Sheepdogs with hypertonic paroxysmal dyskinesia, mainly triggered by exercise and stress, were investigated in a retrospective multi-center investigation aiming to characterize the clinical phenotype and its underlying molecular etiology. Three dogs were closely related and their pedigree suggested autosomal dominant inheritance. Laboratory diagnostic findings included mild lactic acidosis and lactaturia, mild intermittent serum creatine kinase (CK) elevation and hypoglycemia. Electrophysiological tests and magnetic resonance imaging of the brain were unremarkable. A muscle/nerve biopsy revealed a mild type II fiber predominant muscle atrophy. While treatment with phenobarbital, diazepam or levetiracetam did not alter the clinical course, treatment with a gluten-free, home-made fresh meat diet in three dogs or a tryptophan-rich, gluten-free, seafood-based diet, stress-reduction, and acetazolamide or zonisamide in the fourth dog correlated with a partial reduction in, or even a complete absence of, dystonic episodes. The genomes of two cases were sequenced and compared to 654 control genomes. The analysis revealed a case-specific missense variant, c.1658G>A or p.Arg553Gln, in the PCK2 gene encoding the mitochondrial phosphoenolpyruvate carboxykinase 2. Sanger sequencing confirmed that all four cases carried the mutant allele in a heterozygous state. The mutant allele was not found in 117 Shetland Sheepdog controls and more than 500 additionally genotyped dogs from various other breeds. The p.Arg553Gln substitution affects a highly conserved residue in close proximity to the GTP-binding site of PCK2. Taken together, we describe a new form of paroxysmal exercise-induced dyskinesia (PED) in dogs. The genetic findings suggest that PCK2:p.Arg553Gln should be further investigated as putative candidate causal variant. View Full-Text
Keywords: Canis lupus familiaris; whole genome sequencing; dog; mitochondrion; phosphoenolpyruvate-carboxykinase; inborn error of metabolism; precision medicine Canis lupus familiaris; whole genome sequencing; dog; mitochondrion; phosphoenolpyruvate-carboxykinase; inborn error of metabolism; precision medicine
Show Figures

Figure 1

MDPI and ACS Style

Nessler, J.; Hug, P.; Mandigers, P.J.J.; Leegwater, P.A.J.; Jagannathan, V.; Das, A.M.; Rosati, M.; Matiasek, K.; Sewell, A.C.; Kornberg, M.; Hoffmann, M.; Wolf, P.; Fischer, A.; Tipold, A.; Leeb, T. Mitochondrial PCK2 Missense Variant in Shetland Sheepdogs with Paroxysmal Exercise-Induced Dyskinesia (PED). Genes 2020, 11, 774. https://doi.org/10.3390/genes11070774

AMA Style

Nessler J, Hug P, Mandigers PJJ, Leegwater PAJ, Jagannathan V, Das AM, Rosati M, Matiasek K, Sewell AC, Kornberg M, Hoffmann M, Wolf P, Fischer A, Tipold A, Leeb T. Mitochondrial PCK2 Missense Variant in Shetland Sheepdogs with Paroxysmal Exercise-Induced Dyskinesia (PED). Genes. 2020; 11(7):774. https://doi.org/10.3390/genes11070774

Chicago/Turabian Style

Nessler, Jasmin; Hug, Petra; Mandigers, Paul J.J.; Leegwater, Peter A.J.; Jagannathan, Vidhya; Das, Anibh M.; Rosati, Marco; Matiasek, Kaspar; Sewell, Adrian C.; Kornberg, Marion; Hoffmann, Marina; Wolf, Petra; Fischer, Andrea; Tipold, Andrea; Leeb, Tosso. 2020. "Mitochondrial PCK2 Missense Variant in Shetland Sheepdogs with Paroxysmal Exercise-Induced Dyskinesia (PED)" Genes 11, no. 7: 774. https://doi.org/10.3390/genes11070774

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop