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.
Authors: Valberg Stephanie J, Henry Marisa L, Herrick Keely L, Velez-Irizarry Deborah, Finno Carrie J, Petersen Jessica L
Journal: Equine veterinary journal
Summary
# Editorial Summary Type 2 polysaccharide storage myopathy (PSSM2) in Quarter Horses has been attributed to variants in genes associated with myofibrillar myopathy in humans, and commercial genetic tests now market variants P2 (MYOT), P3a/P3b (FLNC), and P4 (MYOZ3) for PSSM2 diagnosis. Valberg and colleagues examined muscle biopsies from 163 histopathologically confirmed PSSM2-affected Quarter Horses and 229 healthy controls, performing desmin staining to assess myofibrillar pathology and genotyping these four genetic variants using pyrosequencing. Crucially, none of the affected horses showed histopathological features of myofibrillar myopathy, and critically, these genetic variants demonstrated no statistically significant association with PSSM2 diagnosis; allele frequencies were nearly identical between affected and control groups, with over half of healthy horses (57%) and affected horses (61%) carrying at least one "disease" variant. Using these genetic markers would misdiagnose 57% of sound horses as affected whilst failing to identify 40% of horses with confirmed PSSM2, rendering the commercial tests unreliable for clinical decision-making. Practitioners should recognise that genetic testing for these variants cannot substitute for muscle biopsy diagnosis and may lead to inappropriate treatment decisions; further investigation into the actual aetiological mechanisms of PSSM2 in Quarter Horses is essential before relying on molecular genetic screening.
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Practical Takeaways
- •Commercial genetic tests for P2, P3, and P4 variants should not be used to diagnose PSSM2 or myofibrillar myopathy in Quarter Horses, as they produce high rates of false positives and false negatives.
- •Histopathological examination (muscle biopsy with desmin staining) remains the gold standard for PSSM2 diagnosis; genetic testing alone is not reliable for clinical decision-making.
- •Owners and practitioners should be cautious about making breeding or management decisions based solely on these commercial genetic tests, as the presence of variants does not correlate with disease status.
Key Findings
- •Histopathological features of myofibrillar myopathy were absent in all 392 Quarter Horses examined, including those with PSSM2 diagnosis.
- •P2, P3a, P3b, and P4 genetic variants were not associated with histopathological PSSM2 diagnosis (P > 0.05), with variants present in 57% of healthy controls and 61% of PSSM2-affected horses.
- •Commercial genetic tests using these variants would falsely diagnose PSSM2/MFM in 57% of healthy Quarter Horses and fail to diagnose PSSM2 in 40% of horses with confirmed histopathological PSSM2.
- •Receiver operator curve analysis showed poor predictive accuracy for PSSM2 phenotype (AUC = 0.67, 95% CI 0.62-0.72), indicating these genetic tests are unreliable diagnostic tools.