Preventing the transmission of mitochondrial DNA disorders using prenatal or preimplantation genetic diagnosis

Hubert J. M. Smeets*, Suzanne C. E. H. Sallevelt, Jos C. F. M. Dreesen, Christine E. M. de Die-Smulders, Irenaeus F. M. de Coo

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Mitochondrial disorders are among the most common inborn errors of metabolism; at least 15% are caused by mitochondrial DNA(mtDNA) mutations, which occur de novo or are maternally inherited. For familial heteroplasmic mtDNA mutations, the mitochondrial bottleneck defines the mtDNA mutation load in offspring, with an often high or unpredictable recurrence risk. Oocyte donation is a safe option to prevent the transmission of mtDNA disease, but the offspring resulting from oocyte donation are genetically related only to the father. Prenatal diagnosis (PND) is technically possible but usually not applicable because of limitations in predicting the phenotype. For de novo mtDNA point mutations, recurrence risks are low and PND can be offered to provide reassurance regarding fetal health. PND is also the best option for female carriers with low-level mutations demonstrating skewing to 0% or 100%. A fairly new option for preventing the transmission of mtDNA diseases is preimplantation genetic diagnosis (PGD), in which embryos with a mutant load below a mutation-specific or general expression threshold of 18% can be transferred. PGD is currently the best reproductive option for familial heteroplasmic mtDNA point mutations. Nuclear genome transfer and genome editing techniques are currently being investigated and might offer additional reproductive options for specific mtDNA disease cases.
Original languageEnglish
Pages (from-to)29-36
JournalAnnals of the New York Academy of Sciences
Publication statusPublished - 2015


  • mtDNA disease
  • prenatal diagnosis
  • preimplantation genetic diagnosis
  • nuclear transfer


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