Researchers at EquiSeq have developed tests for genetic variants that predispose a horse to Polysaccharide Storage Myopathy type 2 (PSSM2) or Myofibrillar Myopathy (MFM), a subtype of PSSM2. These tests identify horses at risk for developing PSSM2/MFM before they show any symptoms.
A muscle biopsy test shows abnormalities in muscle in PSSM2/MFM and other adult-onset myopathies. A horse that has a negative muscle biopsy result when it is young and relatively free of symptoms may have a positive muscle biopsy result later in life. A genetic test will always give the same result throughout the life of a horse.
No. There are horses with a diagnosis of PSSM2/MFM that do not carry copies of the variants (P2, P3, P4, P8, or K1) identified in these tests. Researchers at EquiSeq are searching for other variants (in different genes) that predispose to PSSM2/MFM.
No. The variants identified in these tests have incomplete penetrance. This means that some horses with one copy of the variants (n/P2, n/P3, n/P4, n/P8, or n/K1) will not show any symptoms, even when well past the usual age of onset. Horses with two copies of the variants (P2/P2, P3/P3, P4/P4, P8/P8, or K1/K1) appear to be more strongly affected.
The P2 variant is a missense allele of MYOT, the gene encoding myotilin. The mutation is MYOT-S323P (chr14:37,818,823 A/G in EquCab3.0). The P3 variant is a pair of closely-linked missense alleles of FLNC, the gene encoding filamin C. The mutations are FLNC-E753K (chr4:83,837,774 G/A in EquCab3.0) and FLNC-A1207T (chr4:83,840,299 G/A in EquCab3.0). The P4 variant is a missense allele of MYOZ3, the gene encoding myozenin 3. The mutation is MYOZ3-S42L (chr14:26,710,261 G/A in EquCab3.0). The P8 and K1 variants are missense alleles of undisclosed genes of known function; mutations in the orthologous human genes are associated with inherited myopathies.