Commercial genetic testing for type 2 polysaccharide storage myopathy and myofibrillar myopathy does not correspond to a histopathological diagnosis

Authors

Stephanie J. Valberg, Michigan State UniversityFollow
C. J. Finno, University of California, DavisFollow
Marisa L. Henry, Michigan State University
Melissa Schott, Michigan State University
Deborah Velez-Irizarry, Michigan State University
Sichong Peng, University of California-DavisFollow
Erica C. McKenzie, Oregon State UniversityFollow
Jessica L. Petersen, University of Nebraska - LincolnFollow

ORCID IDs

Stephanie J. Valberg https://orcid.org/0000-0001-5978-7010

Carrie J. Finno https://orcid.org/0000-0001-5924-0234

Erica C. McKenzie https://orcid.org/0000-0001-8041-5238

Jessica L. Petersen https://orcid.org/0000-0001-5438-8555

Date of this Version

2020

Citation

Equine Vet. J. 2020;00:1–11.

DOI: 10.1111/evj.13345

Comments

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License

Abstract

Background: Commercial genetic tests for type 2 polysaccharide storage myopathy (PSSM2) and myofibrillar myopathy (MFM) have not been validated by peer-review, and formal regulation of veterinary genetic testing is lacking.

Objectives: To compare genotype and allele frequencies of commercial test variants (P variants) in MYOT (P2; rs1138656462), FLNC (P3a; rs1139799323), FLNC (P3b; rs1142918816) and MYOZ3 (P4; rs1142544043) between Warmblood (WB) and Arabian (AR) horses diagnosed with PSSM2/MFM by muscle histopathology, and phenotyped breed-matched controls. To quantify variant frequency in public repositories of ancient and modern horse breeds.

Study design: Cross sectional using archived clinical material and publicly available data.

Methods: We studied 54 control-WB, 68 PSSM2/MFM-WB, 30 control-AR, 30 PSSM2/MFM-AR and 205 public genotypes. Variants were genotyped by pyrosequencing archived DNA. Genotype and allele frequency, and number of variant alleles or loci were compared within breed between controls, PSSM2/MFM combined and MFM or PSSM2 horses considered separately using additive/genotypic and dominant models (Fisher's exact tests). Variant frequencies in modern, early domestic and Przewalski horses were determined from a public data repository.

Results: There was no significant association between any P locus and a histopathological diagnosis of PSSM2/MFM, and no difference between control and myopathic horses in total loci with alternative alleles, or total alternate alleles when PSSM2/ MFM was considered combined or separately as PSSM2 or MFM. For all tests, sensitivity was

Conclusions: Because of the lack of significant association between a histopathological diagnosis of PSSM2 or MFM and the commercial genetic test variants P2, P3 and P4 in WB and AR, we cannot recommend the use of these variant genotypes for selection and breeding, prepurchase examination or diagnosis of a myopathy.