Mitochondrial disease genetics update: recent insights into the molecular diagnosis and expanding phenotype of primary mitochondrial disease

Curr Opin Pediatr. 2018 Dec;30(6):714-724. doi: 10.1097/MOP.0000000000000686.


Purpose of review: Primary mitochondrial disease (PMD) is a genetically and phenotypically diverse group of inherited energy deficiency disorders caused by impaired mitochondrial oxidative phosphorylation (OXPHOS) capacity. Mutations in more than 350 genes in both mitochondrial and nuclear genomes are now recognized to cause primary mitochondrial disease following every inheritance pattern. Next-generation sequencing technologies have dramatically accelerated mitochondrial disease gene discovery and diagnostic yield. Here, we provide an up-to-date review of recently identified, novel mitochondrial disease genes and/or pathogenic variants that directly impair mitochondrial structure, dynamics, and/or function.

Recent findings: A review of PubMed publications was performed from the past 12 months that identified 16 new PMD genes and/or pathogenic variants, and recognition of expanded phenotypes for a wide variety of mitochondrial disease genes.

Summary: Broad-based exome sequencing has become the standard first-line diagnostic approach for PMD. This has facilitated more rapid and accurate disease identification, and greatly expanded understanding of the wide spectrum of potential clinical phenotypes. A comprehensive dual-genome sequencing approach to PMD diagnosis continues to improve diagnostic yield, advance understanding of mitochondrial physiology, and provide strong potential to develop precision therapeutics targeted to diverse aspects of mitochondrial disease pathophysiology.

Publication types

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

MeSH terms

  • Computational Biology / trends
  • DNA, Mitochondrial / genetics*
  • Exome / genetics*
  • Genetic Association Studies
  • Genetic Testing / trends*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mitochondrial Diseases / diagnosis*
  • Mitochondrial Diseases / genetics
  • Molecular Diagnostic Techniques / trends*
  • Mutation
  • Phenotype


  • DNA, Mitochondrial