Frequency and association of mitochondrial genetic variants with neurological disorders

Mitochondrion. 2019 May;46:345-360. doi: 10.1016/j.mito.2018.09.005. Epub 2018 Sep 13.


Mitochondria are small cytosolic organelles and the main source of energy production for the cells, especially in the brain. This organelle has its own genome, the mitochondrial DNA (mtDNA), and genetic variants in this molecule can alter the normal energy metabolism in the brain, contributing to the development of a wide assortment of Neurological Disorders (ND), including neurodevelopmental syndromes, neurodegenerative diseases and neuropsychiatric disorders. These ND are comprised by a heterogeneous group of syndromes and diseases that encompass different cognitive phenotypes and behavioral disorders, such as autism, Asperger's syndrome, pervasive developmental disorder, attention deficit hyperactivity disorder, Huntington disease, Leigh Syndrome and bipolar disorder. In this work we carried out a Systematic Literature Review (SLR) to identify and describe the mitochondrial genetic variants associated with the occurrence of ND. Most of genetic variants found in mtDNA were associated with Single Nucleotide Polimorphisms (SNPs), ~79%, with ~15% corresponding to deletions, ~3% to Copy Number Variations (CNVs), ~2% to insertions and another 1% included mtDNA replication problems and genetic rearrangements. We also found that most of the variants were associated with coding regions of mitochondrial proteins but were also found in regulatory transcripts (tRNA and rRNA) and in the D-Loop replication region of the mtDNA. After analysis of mtDNA deletions and CNV, none of them occur in the D-Loop region. This SLR shows that all transcribed mtDNA molecules have mutations correlated with ND. Finally, we describe that all mtDNA variants found were associated with deterioration of cognitive (dementia) and intellectual functions, learning disabilities, developmental delays, and personality and behavior problems.

Keywords: Genetic variants; Mitochondrial DNA; Neurodegenerative diseases; Neurodevelopmental syndromes; Neurological disorders; Neuropsychiatric disorders; Systematic literature review.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • DNA, Mitochondrial / genetics*
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Humans
  • Nervous System Diseases / genetics*
  • Nervous System Diseases / pathology*


  • DNA, Mitochondrial