Clinical spectrum in multiple families with primary COQ₁₀ deficiency

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.