2 型多糖贮积性肌病的组织病理学诊断的夸特马中无纤维肌病，且与商业遗传检测无关联。

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.

机构信息

Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.

Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.

出版信息

Equine Vet J. 2023 Mar;55(2):230-238. doi: 10.1111/evj.13574. Epub 2022 Apr 1.

DOI:10.1111/evj.13574

PMID:35288976

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10084132/

Abstract

BACKGROUND

Genetic tests for variants in MYOT (P2; rs1138656462), FLNC (P3a; rs1139799323 or P3b; rs1142918816) and MYOZ3 (P4; rs1142544043) genes are offered commercially to diagnose myofibrillar myopathy (MFM) and type 2 polysaccharide storage myopathy (PSSM2) in Quarter Horses (QH).

OBJECTIVES

To determine if PSSM2-QH has histopathological features of MFM. To compare genotype and allele frequencies of variants P2, P3, P4 between control-QH and PSSM2-QH diagnosed by histopathology.

STUDY DESIGN

Retrospective cross-sectional.

METHODS

The study includes a total of 229 healthy control-QH, 163 PSSM2-QH GYS1 mutation negative. Desmin stains of gluteal/semimembranosus muscle were evaluated. Purported disease alleles P2, P3a, P3b, P4 were genotyped by pyrosequencing. Genotype, allele frequency and total number of variant alleles or loci were compared between phenotypes using additive/genotypic and dominant models and quantitative effects evaluated by multivariable logistic regression.

RESULTS

Histopathological features of MFM were absent in all QH. A P variant allele at any locus was not associated (P > .05) with a histopathological diagnosis of PSSM2 and one or more P variants were common in control-QH (57%) and PSSM2-QH (61%). Allele frequencies (control/PSSM2) were: 0.24/0.21 (P2), 0.07/0.12 (P3a), 0.07/0.11 (P3b) and 0.06/0.08 (P4). P3a and P3b loci were not independent (r = 0.894); and not associated with PSSM2 histopathology comparing the haplotype of both P3a and P3b variants to other haplotypes. A receiver operator curve did not accurately predict the PSSM2 phenotype (AUC = 0.67, 95% CI 0.62-0.72), and there was no difference in the total number of variant loci or total variant allele count between control-QH and PSSM2-QH.

MAIN LIMITATIONS

P3a and P3b were not in complete linkage disequilibrium.

CONCLUSIONS

The P2, P3 and P4 variants in genes associated with human MFM were not associated with PSSM2 in 392 QH. Their use would improperly diagnose PSSM2/MFM in 57% of healthy QH and fail to diagnose PSSM2 in 40% of QH with histopathological evidence of PSSM2.

摘要

背景

MYOT（P2；rs1138656462）、FLNC（P3a；rs1139799323 或 P3b；rs1142918816）和 MYOZ3（P4；rs1142544043）基因中的变异的基因检测可用于商业诊断夸特马（QH）中的肌原纤维肌病（MFM）和 2 型多糖贮积肌病（PSSM2）。

目的

确定 PSSM2-QH 是否具有 MFM 的组织病理学特征。比较通过组织病理学诊断为 PSSM2-QH 的控制-QH 和 PSSM2-QH 中变体 P2、P3、P4 的基因型和等位基因频率。

研究设计

回顾性横断面研究。

方法

本研究共纳入 229 名健康对照-QH 和 163 名 GYS1 突变阴性的 PSSM2-QH。评估臀肌/半膜肌的结蛋白染色。通过焦磷酸测序对假定的疾病等位基因 P2、P3a、P3b、P4 进行基因分型。使用加性/基因型和显性模型比较表型之间的基因型、等位基因频率和变异等位基因或基因座的总数，并通过多变量逻辑回归评估定量效应。

结果

所有 QH 均不存在 MFM 的组织病理学特征。任何基因座的 P 变异等位基因与 PSSM2 的组织病理学诊断无关（P>.05），一个或多个 P 变异在对照-QH（57%）和 PSSM2-QH（61%）中很常见。等位基因频率（对照/PSSM2）为：0.24/0.21（P2）、0.07/0.12（P3a）、0.07/0.11（P3b）和 0.06/0.08（P4）。P3a 和 P3b 基因座不独立（r=0.894）；比较 P3a 和 P3b 变体的单倍型与其他单倍型，与 PSSM2 组织病理学无关。受试者工作特征曲线不能准确预测 PSSM2 表型（AUC=0.67，95%CI 0.62-0.72），并且在对照-QH 和 PSSM2-QH 之间，变异基因座总数或变异等位基因总数没有差异。