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Preimplantation genetic diagnosis in mitochondrial DNA disorders: challenge and success
  1. Suzanne C E H Sallevelt1,
  2. Joseph C F M Dreesen1,3,
  3. Marion Drüsedau1,
  4. Sabine Spierts1,
  5. Edith Coonen1,2,
  6. Florence H J van Tienen1,3,
  7. Ronald J T van Golde2,3,
  8. Irineus F M de Coo4,
  9. Joep P M Geraedts1,3,
  10. Christine E M de Die-Smulders1,3,
  11. Hubert J M Smeets1,3
  1. 1Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, Limburg, Netherlands
  2. 2Department of Obstetrics & Gynaecology Maastricht University Medical Centre, Maastricht University, Maastricht, Limburg, Netherlands
  3. 3School for Developmental Biology, GROW, Maastricht University, Maastricht, Limburg, Netherlands
  4. 4Department of Neurology, Erasmus MC-Sophia Children's Hospital, Rotterdam, Zuid-holland, The Netherlands
  1. Correspondence to Suzanne C E H Sallevelt, Department of Clinical Genetics, Maastricht University Medical Centre, P. Debeyelaan 25, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands; suzanne.sallevelt{at}


Background Mitochondrial or oxidative phosphorylation diseases are relatively frequent, multisystem disorders; in about 15% of cases they are caused by maternally inherited mitochondrial DNA (mtDNA) mutations. Because of the possible severity of the phenotype, the lack of effective treatment, and the high recurrence risk for offspring of carrier females, couples wish to prevent the transmission of these mtDNA disorders to their offspring. Prenatal diagnosis is problematic for several reasons, and concern the often poor correlation between mutation percentages and disease severity and the uncertainties about the representativeness of a fetal sample. A new option for preventing transmission of mtDNA disorders is preimplantation genetic diagnosis (PGD), which circumvents these problems by transferring an embryo below the threshold of clinical expression.

Methods We present the data on nine PGD cycles in four female carriers of mitochondrial diseases: three mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) (m.3243A>G), and one Leigh (m.8993T>G). Our threshold for transfer after PGD is 15% for the m.3243A>G mutation and 30% for the m.8993T>G mutation.

Results All four female carriers produced embryos eligible for transfer. The m.8993T>G mutation in oocytes/embryos showed more skewing than the m.3243A>G. In about 80% of the embryos the mutation load in the individual blastomeres was fairly constant (interblastomere differences <10%). However, in around 11% (in embryos with the m.3243A>G mutation only), the mutation load differed substantially (>15%) between blastomeres of a single embryo, mostly as a result of one outlier. The m.8993T>G carrier became pregnant and gave birth to a healthy son.

Conclusions PGD provides carriers of mtDNA mutations the opportunity to conceive healthy offspring.

  • Clinical genetics
  • Reproductive medicine
  • Neuromuscular disease
  • Diagnostics tests
  • Molecular genetics

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