Preventing the Transmission of Mitochondrial DNA Variants: MRT Emerges as an Alternative
Mitochondrial variants: a hidden threat passed between generations
Mitochondrial DNA (mtDNA) variants are inherited exclusively through the maternal line and can cause serious metabolic disorders in children. Existing diagnostic methods can easily miss variants when their proportion is low, creating considerable uncertainty for family planning.
Limits of existing tests and a new challenge
Preimplantation genetic testing (PGT) and prenatal screening can detect some variant-positive cases. However, in cases of homoplasmy or high levels of heteroplasmy, eggs with a low variant burden are unlikely to be produced, limiting the ability to prevent transmission completely. Gene-editing technologies also face substantial legal restrictions, so clinical application remains a distant prospect.
MRT offers an alternative
Mitochondrial replacement technology (MRT) is an approach intended to prevent variant transmission by transferring nuclear DNA from the mother’s egg or embryo into a donor egg. However, some maternal mitochondria may be transferred along with it. If mitochondria carrying pathogenic mtDNA variants proliferate preferentially, the threshold for disease manifestation could be exceeded. MRT remains experimental and invasive; sufficient scientific and clinical evidence is needed to establish its safety, including long-term follow-up of children born using the technique. There is hope that MRT may be more effective than existing methods.
Implications and outlook
If MRT becomes a standard treatment, it could open a new paradigm for preventing diseases caused by mtDNA variants. Policy and ethical discussions will need to proceed in parallel, but ultimately the approach could allow many families to have children with greater peace of mind.
This review analyzes strategies to prevent or reduce the transmission of diseases caused by pathogenic variants in mitochondrial DNA (mtDNA). Among these, we focus on prenatal screening, preimplantation genetic testing, gene‑editing techniques, other molecular tools, and selected heterologous mitochondrial replacement techniques (MRTs), explaining their status and the uncertainties surrounding their clinical application. After this analysis and review, we recognize the limitations of the efficacy of prenatal and preimplantation genetic testing for mitochondrial DNA pathogenic variants, the legal constraints on gene editing, and the status of mitochondrial replacement techniques. MRTs are a safe and possibly more effective alternative for preventing diseases caused by mitochondrial DNA pathogenic variants.
This research seeks to address the intergenerational transmission of diseases caused by maternally inherited mitochondrial DNA (mtDNA) variants. If mitochondrial replacement technology (MRT) becomes widely available, it could greatly increase families’ chances of having healthy children.