Mitochondrial DNA mutations in human disease
1College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. sd12@columbia.edu
Abstract:
The small, maternally inherited mitochondrial DNA (mtDNA) has turned out to be a Pandora's box of pathogenic mutations: 13 years into the era of "molecular mitochondrial medicine," more than 100 pathogenic point mutations and innumerable rearrangements have been associated with a striking variety of multisystemic as well as tissue-specific human diseases. After reviewing the principles of mitochondrial genetics, we consider disorders due to mutations in genes affecting mitochondrial protein synthesis and disorders due to mutations in protein-coding genes. In contrast to the remarkable progress in our understanding of etiology, pathogenesis is only partially explained by the rules of mitochondrial genetics and remains largely unclear. We review recent progress in prenatal diagnosis, epidemiology, and in the development of animal models harboring mtDNA mutations.
Insights
Mitochondrial DNA (mtDNA) mutations cause numerous human diseases. While genetic causes are increasingly understood, the underlying pathogenesis of these mitochondrial diseases remains largely unclear, despite advances in diagnosis and animal models.
Area of Science:
- Genetics
- Molecular Medicine
- Human Diseases
Background:
- Mitochondrial DNA (mtDNA) harbors numerous pathogenic mutations.
- Over 100 point mutations and rearrangements are linked to human diseases.
- These diseases can be multisystemic or tissue-specific.
Purpose of the Study:
- Review principles of mitochondrial genetics.
- Discuss disorders from mutations affecting mitochondrial protein synthesis and coding genes.
- Highlight progress and remaining challenges in understanding mtDNA mutation-related diseases.
Main Methods:
- Review of scientific literature on mitochondrial genetics.
- Analysis of disorders caused by mtDNA mutations.
- Examination of progress in prenatal diagnosis, epidemiology, and animal models.
Main Results:
- Significant progress in identifying genetic causes of mtDNA disorders.
- Over 100 pathogenic point mutations and rearrangements identified.
- Pathogenesis of mitochondrial diseases is only partially understood.
Conclusions:
- Mitochondrial DNA mutations are a significant cause of human disease.
- Understanding of etiology has advanced, but pathogenesis requires further research.
- Progress in prenatal diagnosis, epidemiology, and animal models aids research.
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