3697G>A in MT-ND1 is a causative mutation in mitochondrial disease

Mitochondrion. 2016 May;28:54-9. doi: 10.1016/j.mito.2016.03.006. Epub 2016 Mar 24.


Mitochondrial diseases are a group of clinically heterogeneous disorders that can be difficult to diagnose. We report a two and a half year old girl with clinical symptoms compatible with Leigh disease but with no definitive diagnosis. Using next generation sequencing we found that mutation 3697G>A was responsible for the patient's clinical symptoms. Corroboration was performed via segregation analysis in mother and sister and by evolutionary analysis that showed that the mutation is located in a highly conserved region across a wide range of species. Functional analyses corroborated the mutation effect and indicated that the pathophysiological alterations were partially restored by Coenzyme Q10. In addition, we proposed that the presence of the mutation at high frequencies causes the phenotype in the patient, while other family members with intermediate levels of heteroplasmy are symptoms-free.

Keywords: Clinical genomics; Heteroplasmy; Leigh disease; Mitochondrial disease; Next Generation Sequencing.

Publication types

  • Case Reports

MeSH terms

  • Child, Preschool
  • DNA, Mitochondrial / chemistry
  • DNA, Mitochondrial / genetics
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Leigh Disease / genetics*
  • NADH Dehydrogenase / genetics*
  • Point Mutation*
  • Ubiquinone / analogs & derivatives
  • Ubiquinone / therapeutic use


  • DNA, Mitochondrial
  • Ubiquinone
  • NADH Dehydrogenase
  • MT-ND1 protein, human
  • coenzyme Q10

Supplementary concepts

  • Maternally Inherited Leigh Syndrome