144 Lack of correspondence between commercial genetic test variants for type 2 polysaccharide storage myopathy and a histopathologic diagnosis in Quarter Horses

Abstract

A diagnosis of type 2 polysaccharide storage myopathy (PSSM2) in Quarter Horse-related breeds (QH) is currently based on the absence of the glycogen synthase 1 ( GYS1) mutation causing type 1 PSSM (PSSM1) and presence of aggregates polysaccharide in myofibers. Recently, genetic tests for PSSM2 have been offered by a commercial company based on variants in the genes myotilin (termed P2), filamin C (P3) and myozenin 3 (P4). The company claims these variants are associated with PSSM2 as phenotyped by clinical signs without regard to muscle histopathology. The purpose of this study was to compare genotype and allele frequencies of commercial test variants (P variants) in MYOT (P2; rs1138656462), FLNC (P3a; rs1139799323 and P3b; rs1142918816) and MYOZ3 (P4; rs1142544043) between Quarter Horses diagnosed with PSSM2 by muscle histopathology and healthy Quarter Horse controls with normal muscle histology (periodic acid Schiff's stain). DNA was isolated from hair bulb, buffy coat, whole blood or muscle tissue samples. Primers were designed and genotyping performed using pyrosequencing. Genotypes at each locus (homozygous reference vs. heterozygous, homozygous alternate) were compared between PSSM2 (n = 54, 7.6 ± 4.2 y) and control horses (n = 121, 9.8 ± 5.7 y) using a Fisher's exact test ( P ≤ 0.05). There was no significant association between any P locus and a histopathological diagnosis of PSSM2. Minor allele frequencies (cases/controls) were: 20%/27% (P2), 13%/10% (P3a), 11%/9% (P3b)/and 11%/10% (P4). The P2 variant was present in 48% of control and 33% of PSSM2 Quarter Horses. In conclusion, the P2, P3a, P3b and P4 commercial test variants appear to be relatively common variants in Quarter Horses not associated with a diagnosis of PSSM2 established by muscle biopsy.