Reacción a "First results on babies born with pioneering technology that reduces risk of mitochondrial disease"

The field of mitochondrial medicine has been eagerly awaiting the results of this study. The robust data describe a real breakthrough for women with a (nearly) homoplasmic pathogenic mitochondrial DNA (mtDNA) variant in terms of their ability to probably have healthy genetically related children. The risk of the children to develop the disease after preimplantation genetic testing is minimal. All gene variants tested require very high heteroplasmy for the disease to manifest, or are typically homoplasmic.

There is an observation in the literature that in a few cases, the mother's mutated DNA is revised. Interestingly, this also involves an LHON mutation (Leber's hereditary optic neuropathy) [Nature 2019, Nature 2016], which is almost always homoplasmic in the population and, according to recent data, has a low penetrance of less than five percent for LHON disease (only five percent of gene carriers also develop the disease; editor's note). In this respect, the selection of mutation carriers for this study with four LHON mutations is not entirely fortunate. The homoplasmy of the LHON variants suggests that they may offer a selective advantage. Since mitochondrial transfer does not eliminate the mutation, there is a risk that the mutation will be passed on to the next generation. This often leads to significant shifts in heteroplasmy, sometimes to the detriment of patients. However, disease-causing variants tend to have a selection pressure.

Human studies show no risk of incompatibility between the donor mtDNA and the parents' nuclear DNA.

There is no newborn screening for mitochondrial DNA mutations. Women are identified as mutation carriers when they or one of their children develop the disease. Prediction or risk assessment for the next generation is difficult for mtDNA mutations in the mother. Many centers for mitochondrial diseases work with the group in Newcastle to provide information about the options available there or to offer preimplantation genetic diagnosis.