Departamento de Neurociências- Laboratório de doenças neuromusculares da Centro Universitário Saúde ABC, Santo Andre, São Paulo, Brazil.
Instituto Ideia Fértil de Saúde Reprodutiva do Centro Universitário Saúde ABC, Santo Andre, São Paulo, Brazil.
PLoS One. 2020 Jul 31;15(7):e0236597. doi: 10.1371/journal.pone.0236597. eCollection 2020.
McArdle disease presents clinical and genetic heterogeneity. There is no obvious association between genotype and phenotype. PYGM (muscle glycogen phosphorylase gene) mRNA expression and its association with clinical, morphological, and genetic aspects of the disease as a set have not been studied previously.
We investigated genetic variation in PYGM considering the number of PTCs (premature termination codon) per sample and compared mRNA expression in skeletal muscle samples from 15 patients with McArdle disease and 16 controls to PTCs number and different aspects of the disease.
The main variant found was c.148C>T (PTC-premature termination codon). Patients with two PTCs showed 42% mRNA expression compared to the control group. Most cases showed an inversely proportional relation among PTCs and mRNA expression. Association between mRNA expression and other aspects of the disease showed no statistically significant difference (p> 0.05).
mRNA expression is not useful as a predictor factor for the prognosis and severity of the disease. Different mechanisms as post-transcriptional events, epigenetics factors or protein function may be involved.
McArdle 病表现出临床和遗传异质性。基因型和表型之间没有明显的关联。肌肉糖原磷酸化酶基因（PYGM）mRNA 表达及其与疾病的临床、形态和遗传方面的关联作为一个整体尚未被研究过。
我们考虑了每个样本中的 PTC（提前终止密码子）数量，研究了 PYGM 的遗传变异，并将 15 例 McArdle 病患者和 16 例对照的骨骼肌样本的 mRNA 表达与 PTC 数量和疾病的不同方面进行了比较。
发现的主要变异是 c.148C>T（PTC-提前终止密码子）。与对照组相比，有两个 PTC 的患者的 mRNA 表达为 42%。大多数病例的 PTC 和 mRNA 表达之间呈反比关系。mRNA 表达与疾病的其他方面之间没有统计学上的显著差异（p>0.05）。
mRNA 表达不能作为疾病预后和严重程度的预测因素。可能涉及不同的机制，如转录后事件、表观遗传学因素或蛋白质功能。
