Genetic and clinical features of Chinese patients with mitochondrial ataxia identified by targeted next-generation sequencing

Aim To characterize the mutations in mitochondrial DNA (mtDNA) and mitochondrion-related nuclear genes (nDNA), and clinical features in Chinese patients with mitochondrial ataxia. Methods Targeted next-generation sequencing (NGS) technology was performed to screen the whole mtDNA sequence and nDNA genes in a cohort of 33 unrelated ataxia patients. Results A total of 5 pedigrees were finally genetically diagnosed as mitochondrial ataxia, with 3 pathogenic mutations (m.8344A>G, m.9176T>C, and m.9185T>C), one likely pathogenic mutation (m.3995A>G) in mtDNA, and one pathogenic mutation (c.1159_1162dupAAGT, p.Ser388Terfs) in PDHA1. The prevalence of mitochondrial ataxia in our patient cohort is 15.2%. In addition, all 4 patients with mtDNA mutations experienced symptoms of ataxia with age at onset ranging from 12 to 39 years (21 +/- 12.2) and developed extrapyramidal symptoms during the disease course. One male patient with pyruvate dehydrogenase deficiency showed an acute intermittent ataxia phenotype. Conclusions Our results implicate that mitochondrial ataxia might not be as rare in Chinese as previously assumed. This study firstly defines the mutations of mitochondrial ataxia in a Chinese population by targeted NGS, which broadens the clinical spectrum of mtDNA mutations and highlights the importance of screening mtDNA and nDNA mutations among undefined ataxia patients.