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

CNS Neurosci Ther. 2019 Jan;25(1):21-29. doi: 10.1111/cns.12972. Epub 2018 May 13.


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.

Keywords: Chinese; ataxia; mitochondria; targeted next-generation sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Asian People / genetics
  • Ataxia / genetics*
  • Ataxia / physiopathology
  • Child
  • Child, Preschool
  • China
  • Cohort Studies
  • DNA, Mitochondrial
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Middle Aged
  • Mitochondria / genetics
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / physiopathology
  • Mutation*
  • Pedigree
  • Phenotype
  • Pyruvate Dehydrogenase (Lipoamide) / genetics
  • Young Adult


  • DNA, Mitochondrial
  • Pyruvate Dehydrogenase (Lipoamide)
  • pyruvate dehydrogenase E1alpha subunit