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Home / Equine Research Bank / Equine Vet J / Absence of myofibrillar myopathy in Quarter Horses with a hi...
Equine veterinary journal2022; 55(2); 230-238; doi: 10.1111/evj.13574

Absence of myofibrillar myopathy in Quarter Horses with a histopathological diagnosis of type 2 polysaccharide storage myopathy and lack of association with commercial genetic tests.

Abstract: Genetic tests for variants in MYOT (P2; rs1138656462), FLNC (P3a; rs1139799323 or P3b; rs1142918816) and MYOZ3 (P4; rs1142544043) genes are offered commercially to diagnose myofibrillar myopathy (MFM) and type 2 polysaccharide storage myopathy (PSSM2) in Quarter Horses (QH). Objective: To determine if PSSM2-QH has histopathological features of MFM. To compare genotype and allele frequencies of variants P2, P3, P4 between control-QH and PSSM2-QH diagnosed by histopathology. Methods: Retrospective cross-sectional. Methods: The study includes a total of 229 healthy control-QH, 163 PSSM2-QH GYS1 mutation negative. Desmin stains of gluteal/semimembranosus muscle were evaluated. Purported disease alleles P2, P3a, P3b, P4 were genotyped by pyrosequencing. Genotype, allele frequency and total number of variant alleles or loci were compared between phenotypes using additive/genotypic and dominant models and quantitative effects evaluated by multivariable logistic regression. Results: Histopathological features of MFM were absent in all QH. A P variant allele at any locus was not associated (P > .05) with a histopathological diagnosis of PSSM2 and one or more P variants were common in control-QH (57%) and PSSM2-QH (61%). Allele frequencies (control/PSSM2) were: 0.24/0.21 (P2), 0.07/0.12 (P3a), 0.07/0.11 (P3b) and 0.06/0.08 (P4). P3a and P3b loci were not independent (r  = 0.894); and not associated with PSSM2 histopathology comparing the haplotype of both P3a and P3b variants to other haplotypes. A receiver operator curve did not accurately predict the PSSM2 phenotype (AUC = 0.67, 95% CI 0.62-0.72), and there was no difference in the total number of variant loci or total variant allele count between control-QH and PSSM2-QH. Conclusions: P3a and P3b were not in complete linkage disequilibrium. Conclusions: The P2, P3 and P4 variants in genes associated with human MFM were not associated with PSSM2 in 392 QH. Their use would improperly diagnose PSSM2/MFM in 57% of healthy QH and fail to diagnose PSSM2 in 40% of QH with histopathological evidence of PSSM2. Unassigned: Testes genéticos para detecção das mutações MYOT (P2; rs1138656462), FLNC (P3a; rs1139799323 ou P3b; rs1142918816) e MYOZ3 (P4; rs1142544043) são oferecidos comercialmente para diagnosticar miopatia miofibrilar (MMF) e miopatia por acúmulo de polissacarídeo tipo 2 (PSSM2) em cavalos Quarto de Milha (QM). HIPÓTESES/OBJETIVOS: Determinar se PSSM2-QM tem características similares à MMF. Comparar o genótipo e a frequência dos alelos variantes P2, P3, e P4 entre cavalos QM controle, e PSSM2-QM diagnosticados por histologia. MÉTODOS: 229 cavalos QH saudáveis como controle, e 163 PSSM2-QM positivos na histologia e negativos para a mutação GYS1. Methods: Amostras dos músculos glúteo/semimembranoso foram avaliadas após coloração com desmina. Os pretensos genes alelos P2, P3a, P3b e P4 foram genotipados por pirosequenciamento. Genótipo, frequência alélica, e número total de variância alélica ou loci foram comparados entre os fenótipos usado aditivo/genotípico e modelos dominantes e efeitos quantitativos através de regressão logística multivariável. Results: Características histopatológicas de MMF não foram encontradas em nenhum QM. Uma variante alélica P em qualquer uma dos loci não foi associada (P > .05) com o diagnóstico histopatológicos de PSSM2 e uma ou mais variante P foram comuns em QM controles (57%) e PSSM2-QM (61%). Frequência alélica (controle/PSSM2) foram: 0.24/0.21 (P2), 0.07/0.12 (P3a), 0.07/0.11 (P3b), e 0.06/0.08 (P4). P3a e P3b loci não foram independentes (r  = 0.894); e não foram associados com achados histopatológicos de PSSM quando comparando o haplótipo de ambas as variantes P3a e P3b com os outros haplótipos. A curva característica de operação do receptor não previu acuradamente o fenótipo PSSM2 (AUC = 0.67, 95% IC 0.62-0.72), e não houve diferença no número dotal de variantes no loci ou na contagem de variantes alélicas total entre QM controles e PSSM2-QM. PRINCIPAIS LIMITAÇÕES: P3a e P3b não estavam em desequilíbrio de ligação. CONCLUSÕES: As variantes P2, P3 e P4 em genes associados com MMF em humanos não foram associadas com PSSM em 392 QM. O seu uso diagnosticaria impropriamente PSSM2 e MMF em 57% dos cavalos saudáveis utilizados como controle e não diagnosticaria PSSM2 em 40% dos QM com evidência histológica de PSSM2.
© 2022 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
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Publication Date: 2022-04-01 PubMed ID: 35288976PubMed Central: PMC10084132DOI: 10.1111/evj.13574Google Scholar: Lookup
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Summary

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The research investigates the use of commercial genetic tests for the diagnosis of myofibrillar myopathy (MFM) and type 2 polysaccharide storage myopathy (PSSM2) in Quarter Horses. The study finds that the genetic variants being tested for are not associated with PSSM2 and their use could lead to improper diagnosis in both healthy and PSSM2-affected horses.

Objective and Methodology

  • Researchers aimed to ascertain whether the histopathological features of PSSM2 in Quarter Horses (QH) resembled those of myofibrillar myopathy (MFM). They also compared genotype and allele frequencies of certain variants (P2, P3, P4) between control (healthy) Quarter Horses and PSSM2-affected Quarter Horses diagnosed through histopathology.
  • This retrospective, cross-sectional study involved a comparison between 229 healthy control Quarter Horses and 163 PSSM2-affected, GYS1 mutation negative Quarter Horses.
  • Desmin staining of gluteal/semimembranosus muscle tissues was conducted to evaluate muscle structure and possible disease manifestation.
  • The purported disease-related variants (P2, P3a, P3b, P4) were genotyped by pyrosequencing. This technique was used to determine the sequence of alleles in the DNA samples, thereby identifying potential genetic variants associated with the diseases.
  • Researchers used additive/genotypic and dominant models, as well as multivariable logistic regression to compare genotype, allele frequency and total number of variant alleles or loci (the locations of genes on a chromosome) between the phenotypes.

Major Findings

  • No MFM features were found in the examined Quarter Horses during histopathological analysis.
  • A P variant allele at any locus was not associated with a histopathological diagnosis of PSSM2. These P variant alleles were common in both control (57%) and PSSM2-affected Quarter Horses (61%).
  • The frequency of allele variants was as follows: P2 (0.24 in control and 0.21 in PSSM2), P3a (0.07 in control and 0.12 in PSSM2), P3b (0.07 in control and 0.11 in PSSM2), and P4 (0.06 in control and 0.08 in PSSM2).
  • P3a and P3b loci were not independent and were not associated with PSSM2 when comparing their haplotype (the combination of alleles) with other haplotypes.
  • A receiver operator curve did not accurately predict the PSSM2 phenotype (AUC = 0.67, 95% Confidence Interval 0.62-0.72). There was no significant difference in the total number of variant loci or total variant allele count between control Quarter Horses and PSSM2-affected Quarter Horses.

Conclusions

  • The P3a and P3b were not in full linkage disequilibrium, which means they do not always inherit together.
  • The P2, P3, and P4 variants in genes associated with human MFM were not associated with PSSM2 in the researched group of 392 Quarter Horses.
  • Utilizing these variants for diagnosis risks improper identification of PSSM2/MFM in 57% of healthy Quarter Horses and a failure to diagnose PSSM2 in 40% of Quarter Horses confirmed to have PSSM2 through histopathological evidence.

Cite This Article

APA
Valberg SJ, Henry ML, Herrick KL, Velez-Irizarry D, Finno CJ, Petersen JL. (2022). Absence of myofibrillar myopathy in Quarter Horses with a histopathological diagnosis of type 2 polysaccharide storage myopathy and lack of association with commercial genetic tests. Equine Vet J, 55(2), 230-238. https://doi.org/10.1111/evj.13574

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 55
Issue: 2
Pages: 230-238

Researcher Affiliations

Valberg, Stephanie J
  • Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
Henry, Marisa L
  • Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
Herrick, Keely L
  • Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
Velez-Irizarry, Deborah
  • Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
Finno, Carrie J
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
Petersen, Jessica L
  • Department of Animal Science, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.

MeSH Terms

  • Humans
  • Horses
  • Animals
  • Retrospective Studies
  • Cross-Sectional Studies
  • Muscle, Skeletal / pathology
  • Myopathies, Structural, Congenital / pathology
  • Myopathies, Structural, Congenital / veterinary
  • Polysaccharides
  • Horse Diseases / diagnosis
  • Horse Diseases / genetics
  • Horse Diseases / pathology

Grant Funding

  • L40 TR001136 / NCATS NIH HHS
  • American Quarter Horse Association
  • Mary Anne McPhail Endowment at Michigan State University
  • L40 TR001136 / Foundation for the National Institutes of Health

Conflict of Interest Statement

SJ Valberg runs the Neuromuscular Diagnostic Laboratory at Michigan State University that processes muscle biopsies through the Michigan State Veterinary Diagnostic Laboratory. She has no personal financial interest in muscle biopsy submissions. SJ Valberg with other colleagues license commercial laboratories to perform type 1 PSSM testing and personally receives royalties. Some horses in the present study may have been tested by their owners in licensed PSSM1 laboratories. Other authors report no competing interests.

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Citations

This article has been cited 2 times.
  1. Lindsay-McGee V, Massey C, Li YT, Clark EL, Psifidi A, Piercy RJ. Characterisation of phenotypic patterns in equine exercise-associated myopathies. Equine Vet J 2025 Mar;57(2):347-361.
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