Coenzyme Q_10/COQ₁₀, an essential cofactor in the electron‐transport chain is involved in ATP production. Primary COQ₁₀ deficiency is clinically and genetically a heterogeneous group of mitochondrial disorders caused by defects in the COQ₁₀ synthesis pathway. Its mode of inheritance is autosomal recessive and it is characterized by metabolic abnormalities and multisystem involvement including neurological features. Mutations in 10 genes have been identified concerning this group of diseases, so far. Among those, variants of the COQ7 gene are very rare and confined to three patients with Asian ancestry. Here, we present the clinical features and results of whole‐exome sequencing (WES) of three Iranian unrelated families affected by primary COQ₁₀ deficiency. Three homozygous variants in COQ2, COQ4, and COQ7 genes were identified. Candidate variants of the COQ2 and COQ4 genes were novel and associated with the cerebellar signs and multisystem involvement, whereas, the known variant in COQ7 was associated with a mild phenotype that was initially diagnosed as hereditary spastic paraplegia (HSP). This variant has already been reported in a Canadian girl with similar presentations that also originated from Iran suggesting both patients may share a common ancestor. Due to extensive heterogeneity in this group of disorders, and overlap with other mitochondrial/neurological disorders, WES may be helpful to distinguish primary coenzyme Q₁₀ deficiency from other similar conditions. Given that some features of primary coenzyme Q₁₀ deficiency may improve with exogenous COQ₁₀, early diagnosis is very important.

中文翻译：

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原发性COQ10缺乏症的多个家庭的临床表现

辅酶Q _{10 /} COQ ₁₀是电子传输链中必不可少的辅助因子，与ATP的产生有关。在临床和遗传上，原发性COQ ₁₀缺乏症是由COQ ₁₀合成途径中的缺陷引起的线粒体疾病异质性组。它的遗传方式是常染色体隐性遗传，其特征是代谢异常和涉及神经系统特征的多系统参与。到目前为止，已经鉴定出与这组疾病有关的10个基因的突变。其中，COQ7的变体该基因非常罕见，仅限于三名亚洲血统患者。在这里，我们介绍了受原发性COQ ₁₀缺乏症影响的三个伊朗无关家庭的临床特征和全外显子测序结果。确定了COQ2，COQ4和COQ7基因的三个纯合变异体。COQ2和COQ4基因的候选变体是新颖的，并与小脑体征和多系统参与有关，而COQ7中的已知变体与最初诊断为遗传性痉挛性截瘫（HSP）的轻度表型有关。已经有一位来自伊朗的相似女孩的加拿大女孩曾报道过这种变异，这表明这两名患者可能有共同的祖先。由于这一类疾病的广泛异质性，并与其他线粒体/神经疾病重叠，WES可能有助于将原辅酶Q ₁₀缺乏症与其他类似疾病区分开。鉴于原辅酶Q ₁₀缺乏的某些特征可通过外源COQ ₁₀改善，因此早期诊断非常重要。