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Home / Equine Research Bank / PLoS One / Allele copy number and underlying pathology are associated w...
PloS one2012; 7(7); e42317; doi: 10.1371/journal.pone.0042317

Allele copy number and underlying pathology are associated with subclinical severity in equine type 1 polysaccharide storage myopathy (PSSM1).

Abstract: Equine type 1 polysaccharide storage myopathy (PSSM1), a common glycogenosis associated with an R309H founder mutation in the glycogen synthase 1 gene (GYS1), shares pathological features with several human myopathies. In common with related human disorders, the pathogenesis remains unclear in particular, the marked phenotypic variability between affected animals. Given that affected animals accumulate glycogen and alpha-crystalline polysaccharide within their muscles, it is possible that physical disruption associated with the presence of this material could exacerbate the phenotype. The aim of this study was to compare the histopathological changes in horses with PSSM1, and specifically, to investigate the hypothesis that the severity of underlying pathology, (e.g. vacuolation and inclusion formation) would (1) be higher in homozygotes than heterozygotes and (2) correlate with clinical severity. Resting and post-exercise plasma creatine kinase (CK) and aspartate aminotransferase (AST) enzyme activity measurements and muscle pathology were assessed in matched cohorts of PSSM1 homozygotes, heterozygotes or control horses. Median (interquartile range (IR)) resting CK activities were 364 (332-764) U/L for homozygotes, 301 (222-377) U/L for heterozygotes and 260 (216-320) U/L for controls, and mean (+/- SD) AST activity for homozygotes were 502 (+/116) U/L, for heterozygotes, 357 (+/-92) U/L and for controls, 311 (+/-64) U/L and were significantly different between groups (P = 0.04 and P = 0.01 respectively). Resting plasma AST activity was significantly associated with the severity of subsarcolemmal vacuolation (rho = 0.816; P = 0.01) and cytoplasmic inclusions (rho = 0.766; P = 0.01). There were fewer type 2× and more type 2a muscle fibres in PSSM1-affected horses. Our results indicate that PSSM1 has incomplete dominance. Furthermore, the association between plasma muscle enzyme activity and severity of underlying pathology suggests that physical disruption of myofibres may contribute to the myopathic phenotype. This work provides insight into PSSM1 pathogenesis and has implications for related human glycogenoses.
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Publication Date: 2012-07-31 PubMed ID: 22860112PubMed Central: PMC3409190DOI: 10.1371/journal.pone.0042317Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This is a research study on equine type 1 polysaccharide storage myopathy (PSSM1), a common genetic disorder affecting horses. The study explores the relationship between instances of PSSM1 affecting the functionality of horses’ muscle tissues and the severity of this disorder’s symptoms, focusing on a result showing a correlation between enzyme activity in plasma muscle and the severity of the underlying pathology.

Objective of the Study

  • The main purpose of the study was to investigate the changes in the muscle tissues of horses affected by PSSM1 and explore the potential relationship between these changes and the severity of the disease’s symptoms.
  • A secondary goal was to examine whether PSSM1 dominant or recessive gene occurrences reflected a difference in disease severity.

Methodology

  • The research team evaluated resting and post-exercise plasma enzyme activity and assessed muscle pathology in a controlled set of affected and non-affected horses.
  • The study specifically measured the enzyme activities of creatine kinase (CK) and aspartate aminotransferase (AST).
  • For each group of PSSM1 homozygotes, heterozygotes, and control horses, the team identified the median and mean enzyme activity levels and compared these between the groups.

Findings

  • The study found significant differences in plasma muscle enzyme activity between affected and non-affected horses.
  • AST activity was associated with the severity of vacuolation (formation of small cavities in a cell’s structure) and cytoplasmic inclusions (irregular elements within a cell’s cytoplasm).
  • The team observed fewer type 2x and more type 2a muscle fibers in affected horses, indicating influences on tissue composition and functionality.

Implications

  • These findings suggest that the underlying physical disruption of muscle cells could be a contributing factor to the symptoms of PSSM1.
  • The research indicates that the PSSM1 gene exhibits incomplete dominance, meaning the symptoms can vary significantly in severity across different horses.
  • This study could offer insights into the pathogenesis of PSSM1 and related glycogen storage diseases in humans.

Cite This Article

APA
Naylor RJ, Livesey L, Schumacher J, Henke N, Massey C, Brock KV, Fernandez-Fuente M, Piercy RJ. (2012). Allele copy number and underlying pathology are associated with subclinical severity in equine type 1 polysaccharide storage myopathy (PSSM1). PLoS One, 7(7), e42317. https://doi.org/10.1371/journal.pone.0042317

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 7
Issue: 7
Pages: e42317
PII: e42317

Researcher Affiliations

Naylor, Rosie J
  • Comparative Neuromuscular Diseases Laboratory, The Royal Veterinary College, London, United Kingdom.
Livesey, Leanda
    Schumacher, John
      Henke, Nicole
        Massey, Claire
          Brock, Kenny V
            Fernandez-Fuente, Marta
              Piercy, Richard J

                MeSH Terms

                • Alleles
                • Animals
                • Biopsy
                • Gene Dosage
                • Horse Diseases / genetics
                • Horse Diseases / metabolism
                • Horse Diseases / pathology
                • Horses
                • Immunohistochemistry
                • Muscular Diseases / genetics
                • Muscular Diseases / metabolism
                • Muscular Diseases / pathology
                • Polysaccharides / metabolism

                Conflict of Interest Statement

                The authors have declared that no competing interests exist.

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                Citations

                This article has been cited 2 times.
                1. Laforêt P, Oldfors A, Malfatti E, Vissing J. 251st ENMC international workshop: Polyglucosan storage myopathies 13-15 December 2019, Hoofddorp, the Netherlands.. Neuromuscul Disord 2021 May;31(5):466-477.
                  doi: 10.1016/j.nmd.2021.01.010pubmed: 33602551google scholar: lookup
                2. Maile CA, Hingst JR, Mahalingan KK, O'Reilly AO, Cleasby ME, Mickelson JR, McCue ME, Anderson SM, Hurley TD, Wojtaszewski JFP, Piercy RJ. A highly prevalent equine glycogen storage disease is explained by constitutive activation of a mutant glycogen synthase.. Biochim Biophys Acta Gen Subj 2017 Jan;1861(1 Pt A):3388-3398.
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