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Prenatal diagnosis of myopathy, encephalopathy, lactic acidosis, and stroke-like syndrome: contribution to understanding mitochondrial DNA segregation during human embryofetal development
  1. C Bouchet1,
  2. J Steffann1,4,
  3. J Corcos3,
  4. S Monnot1,2,
  5. V Paquis2,
  6. A Rötig1,4,
  7. S Lebon1,
  8. P Levy1,
  9. G Royer1,
  10. I Giurgea1,
  11. N Gigarel1,
  12. A Benachi3,
  13. Y Dumez3,
  14. A Munnich1,4,
  15. J P Bonnefont1,4
  1. 1Department of Genetics, Hôpital Necker-Enfants Malades, Paris, France
  2. 2Department of Genetics, Hôpital Archet 2, Nice
  3. 3Department of Obstetrics, Hôpital Necker-Enfants Malades, Paris
  4. 4Unité INSERMU781, Paris
  1. Correspondence to:
 J P Bonnefont
 Unité INSERMU781, Paris 75015, France;bonnefon{at}


Introduction: Myopathy, encephalopathy, lactic acidosis, and stroke-like (MELAS) syndrome, a maternally inherited disorder that is among the most common mitochondrial DNA (mtDNA) diseases, is usually associated with the m.3242A>G mutation of the mitochondrial tRNAleu gene. Very few data are available with respect to prenatal diagnosis of this serious disease. The rate of mutant versus wild-type mtDNA (heteroplasmy) in fetal DNA is indeed considered to be a poor indicator of postnatal outcome.

Materials and methods: Taking advantage of a novel semi-quantitative polymerase chain reaction test for m.3243A>G mutant load assessment, we carried out nine prenatal diagnoses in five unrelated women, using two different fetal tissues (chorionic villi v amniocytes) sampled at two or three different stages of pregnancy.

Results: Two of the five women, although not carrying m.3243A>G in blood or extra-blood tissues, were, however, considered at risk for transmission of the mutation, as they were closely related to MELAS-affected individuals. The absence of 3243A>G in the blood of first degree relatives was associated with no mutated mtDNA in the cardiovascular system (CVS) or amniocytes, and their three children are healthy, with a follow-up of 3 months–3 years. Among the six fetuses from the three carrier women, three were shown to be homoplasmic (0% mutant load), the remaining three being heteroplasmic, with a mutant load ranging from 23% to 63%. The fetal mutant load was fairly stable at two or three different stages of pregnancy in CVS and amniocytes. Although pregnancy was terminated in the case of the fetus with a 63% mutant load, all other children are healthy with a follow-up of 3 months–6 years.

Conclusion: These data suggest that a prenatal diagnosis for MELAS syndrome might be helpful for at-risk families.

  • CVS, chorionic villous sampling
  • MELAS, myopathy, encephalopathy, lactic acidosis, and stroke-like
  • mtDNA, mitochondrial DNA
  • PCR, polymerase chain reaction

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  • Published Online First 11 May 2006

  • Competing interests: None declared.