Commercial genetic testing for type 2 polysaccharide storage myopathy and myofibrillar myopathy does not correspond to a histopathological diagnosis.
Authors: Valberg Stephanie J, Finno Carrie J, Henry Marisa L, Schott Melissa, Velez-Irizarry Deborah, Peng Sichong, McKenzie Erica C, Petersen Jessica L
Journal: Equine veterinary journal
Summary
# Editorial Summary: Genetic Testing for PSSM2 and MFM Does Not Support Commercial Use Commercial genetic tests marketed for polysaccharide storage myopathy type 2 (PSSM2) and myofibrillar myopathy (MFM) lack rigorous validation, prompting Valberg and colleagues to investigate whether four commonly tested genetic variants (P2, P3a, P3b, and P4) actually correlate with histopathological muscle disease in Warmbloods and Arabians. The researchers compared genotype frequencies between 98 Warmbloods and 60 Arabians with confirmed PSSM2 or MFM diagnosed through muscle biopsy against 84 breed-matched healthy controls, analysing archived DNA and publicly available equine genomes spanning ancient to modern horses. Crucially, none of the four variants showed statistically significant association with myopathic diagnosis in either breed—sensitivity was below 33% for all tests—and no difference emerged between diseased and control horses when considering total variant burden across all loci. All variants existed in ancient horse populations dating back thousands of years, suggesting they represent normal genetic variation rather than disease-causing mutations. These findings have immediate practical implications: currently available genetic tests for PSSM2 and MFM cannot reliably identify affected horses, guide breeding decisions, or support prepurchase evaluations, meaning practitioners should not rely on positive results to diagnose myopathy or recommend against breeding carriers without additional clinical and histopathological evidence.
Read the full abstract on PubMed
Practical Takeaways
- •Do not use P2, P3, or P4 variant genotypes for breeding selection, prepurchase examination, or diagnosis of PSSM2 or MFM—these commercial tests lack validation and cannot reliably identify affected horses
- •Muscle histopathology remains the gold standard for PSSM2/MFM diagnosis; genetic testing alone is insufficient and may provide false reassurance or false positives
- •Request peer-reviewed validation and regulatory oversight before adopting any new equine genetic tests, as this study demonstrates commercial tests can be marketed without scientific evidence of clinical utility
Key Findings
- •No significant association found between any of the four commercial genetic test variants (P2, P3a, P3b, P4) and histopathological diagnosis of PSSM2/MFM in Warmblood or Arabian horses
- •Sensitivity of all commercial tests was <0.33, indicating poor diagnostic accuracy
- •All P variants were present in early domestic horses (400-5500 years old) and P2 in Przewalski horses, suggesting variants are ancestral and not disease-specific
- •Allele frequencies did not differ significantly between control and myopathic horses when PSSM2/MFM was analyzed combined or separately