Biallelic mutations in the C1QBP gene have been associated with mitochondrial cardiomyopathy and combined respiratory‐chain deficiencies, with variable onset (including intrauterine or neonatal forms), phenotypes, and severity. We studied two unrelated adult patients from consanguineous families, presenting with progressive external ophthalmoplegia (PEO), mitochondrial myopathy, and without any heart involvement. Muscle biopsies from both patients showed typical mitochondrial alterations and the presence of multiple mitochondrial DNA deletions, whereas biochemical defects of the respiratory chain were present only in one subject. Using next‐generation sequencing approaches, we identified homozygous mutations in C1QBP. Immunoblot analyses in patients' muscle samples revealed a strong reduction in the amount of the C1QBP protein and varied impairment of respiratory chain complexes, correlating with disease severity. Despite the original study indicated C1QBP mutations as causative for mitochondrial cardiomyopathy, our data indicate that mutations in C1QBP have to be considered in subjects with PEO phenotype or primary mitochondrial myopathy and without cardiomyopathy.

中文翻译：

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C1QBP 中的纯合突变导致进行性外眼肌麻痹 (PEO) 和线粒体肌病伴多个 mtDNA 缺失。

C1QBP基因中的双等位基因突变与线粒体心肌病和联合呼吸链缺陷相关，其发病（包括宫内或新生儿形式）、表型和严重程度不同。我们研究了来自近亲家庭的两名不相关的成年患者，他们表现为进行性眼外肌麻痹 (PEO)、线粒体肌病，并且没有任何心脏受累。两名患者的肌肉活检显示典型的线粒体改变和多个线粒体 DNA 缺失的存在，而呼吸链的生化缺陷仅存在于一名受试者中。使用下一代测序方法，我们确定了C1QBP中的纯合突变. 患者肌肉样本中的免疫印迹分析显示，C1QBP 蛋白的量显着减少，呼吸链复合物的各种损伤与疾病严重程度相关。尽管最初的研究表明C1QBP突变是线粒体心肌病的病因，但我们的数据表明，在具有 PE​​O表型或原发性线粒体肌病且没有心肌病的受试者中必须考虑C1QBP的突变。