ArticleHuman reproduction (Oxford, England)2013
Preventing the transmission of pathogenic mitochondrial DNA mutations: Can we achieve long-term benefits from germ-line gene transfer?
Article in Human reproduction (Oxford, England), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Sequencing and characterizing human mitochondrial genomes in the biobank-based genomic research paradigm.Science China. Life sciences · 2025Review
- Modeling-based prediction tools for preimplantation genetic testing of mitochondrial DNA diseases: estimating symptomatic thresholds, risk, and chance of success.Journal of assisted reproduction and genetics · 2023Article
- Avoiding misleading estimates using mtDNA heteroplasmy statistics to study bottleneck size and selection.G3 (Bethesda, Md.) · 2023Article
- Natural and Artificial Mechanisms of Mitochondrial Genome Elimination.Life (Basel, Switzerland) · 2021Review
- Current progress in the therapeutic options for mitochondrial disorders.Physiological research · 2020Article
- Impact of pharmacological agents on mitochondrial function: a growing opportunity?Biochemical Society transactions · 2019Review
- Overcoming bioethical, legal, and hereditary barriers to mitochondrial replacement therapy in the USA.Journal of assisted reproduction and genetics · 2019Article
- Mitochondrial matters: Mitochondrial bottlenecks, self-assembling structures, and entrapment in the female germline.Stem cell research · 2017Review
- Mitochondrial Modification Techniques and Ethical Issues.Journal of clinical medicine · 2017Article
- Mitochondrial replacement approaches: challenges for clinical implementation.Genome medicine · 2016Article
- Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease.Nature · 2016Article
- CRISPR/Cas9 and mitochondrial gene replacement therapy: promising techniques and ethical considerations.American journal of stem cells · 2016Review
- Mitochondrial replacement therapy in reproductive medicine.Trends in molecular medicine · 2015Review
- Mitochondrial replacement therapies can circumvent mtDNA-based disease transmission.Cell metabolism · 2014Article
- Article
- Mitochondrial DNA genetics and the heteroplasmy conundrum in evolution and disease.Cold Spring Harbor perspectives in biology · 2013Review
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Mitochondrial medicine is one of the few areas of genetic disease where germ-line transfer is being actively pursued as a treatment option. All of the germ-line transfer methods currently under development involve some carry-over of the maternal mitochondrial DNA (mtDNA) heteroplasmy, potentially delivering the pathogenic mutation to the offspring. Rapid changes in mtDNA heteroplasmy have been observed within a single generation, and so any 'leakage' of mutant mtDNA could lead to mtDNA disease in future generations, compromising the reproductive health of the first generation, and leading to repeated interventions in subsequent generations. To determine whether this is a real concern, we developed a model of mtDNA heteroplasmy inheritance by studying 87 mother-child pairs, and predicted the likely outcome of different levels of 'mutant mtDNA leakage' on subsequent maternal generations. This showed that, for a clinical threshold of 60%, reducing the proportion of mutant mtDNA to <5% dramatically reduces the chance of disease recurrence in subsequent generations, but transmitting >5% mutant mtDNA was associated with a significant chance of disease recurrence. Mutations with a lower clinical threshold were associated with a higher risk of recurrence. Our findings provide reassurance that, at least from an mtDNA perspective, methods currently under development have the potential to effectively eradicate pathogenic mtDNA mutations from subsequent generations.
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Registered trials
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