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首页> 外文期刊>Human mutation >Missense mutations have unexpected consequences: The McArdle disease paradigm
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Missense mutations have unexpected consequences: The McArdle disease paradigm

机译：密码突变具有意想不到的后果：Mcardle疾病范式

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Abstract McArdle disease is a disorder of muscle glycogen metabolism caused by mutations in the PYGM gene, encoding for the muscle‐specific isoform of glycogen phosphorylase (M‐GP). The activity of this enzyme is completely lost in patients’ muscle biopsies, when measured with a standard biochemical test which, does not allow to determine M‐GP protein levels. We aimed to determine M‐GP protein levels in the muscle of McArdle patients, by studying biopsies of 40 patients harboring a broad spectrum of PYGM mutations and 22 controls. Lack of M‐GP protein was found in muscle in the vast majority (95%) of patients, irrespective of the PYGM genotype, including those carrying missense mutations, with few exceptions. M‐GP protein biosynthesis is not being produced by PYGM mutations inducing premature termination codons (PTC), neither by most PYGM missense mutations. These findings explain the lack of PYGM genotype–phenotype correlation and have important implications for the design of molecular‐based therapeutic approaches.
机译：摘要麦卡尔氏病是一种由PyGM基因突变引起的肌肉糖原代谢紊乱，编码糖原磷酸化酶（M-GP）的肌肉特异性同种型。当用标准生化测试测量时，这种酶的活性在患者的肌肉活组织检查中完全丧失，不允许确定M-GP蛋白水平。我们旨在通过研究40名患者患有广谱蛋白突变和22例对照的患者的活组织检查，确定Mcardle患者肌肉中的M-GP蛋白水平。绝大多数（95％）患者中肌肉中发现缺乏M-GP蛋白，无论pygm基因型如何，包括携带携带的小畸形突变，少数例外情况。 M-GP蛋白生物合成未被诱导过早终止密码子（PTC），既不是由大多数PyGM的畸变突变都没有产生。这些发现解释了缺乏PyGM基因型 - 表型相关性，对基于分子的治疗方法的设计具有重要意义。

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