RT Journal Article SR Electronic T1 Segregation of mitochondrial DNA mutations in the human placenta: implication for prenatal diagnosis of mtDNA disorders JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP jmedgenet-2017-104615 DO 10.1136/jmedgenet-2017-104615 A1 Pauline Vachin A1 Elodie Adda-Herzog A1 Gihad Chalouhi A1 Caroline Elie A1 Marlène Rio A1 Sophie Rondeau A1 Nadine Gigarel A1 Fabienne Jabot Hanin A1 Sophie Monnot A1 Roxana Borghese A1 Joana Bengoa A1 Yves Ville A1 Agnes Rotig A1 Arnold Munnich A1 Jean-Paul Bonnefont A1 Julie Steffann YR 2017 UL http://jmg.bmj.com/content/early/2017/07/27/jmedgenet-2017-104615.abstract AB Background Mitochondrial DNA (mtDNA) disorders have a high clinical variability, mainly explained by variation of the mutant load across tissues. The high recurrence risk of these serious diseases commonly results in requests from at-risk couples for prenatal diagnosis (PND), based on determination of the mutant load on a chorionic villous sample (CVS). Such procedures are hampered by the lack of data regarding mtDNA segregation in the placenta.The objectives of this report were to determine whether mutant loads (1) are homogeneously distributed across the whole placentas, (2) correlate with those in amniocytes and cord blood cells and (3) correlate with the mtDNA copy number.Methods We collected 11 whole placentas carrying various mtDNA mutations (m.3243A>G, m.8344A>G, m.8993T>G, m.9185T>C and m.10197G>A) and, when possible, corresponding amniotic fluid samples (AFSs) and cord blood samples. We measured mutant loads in multiple samples from each placenta (n= 6–37), amniocytes and cord blood cells, as well as total mtDNA content in placenta samples.Results Load distribution was homogeneous at the sample level when average mutant load was low (<20%) or high (>80%) at the whole placenta level. By contrast, a marked heterogeneity was observed (up to 43%) in the intermediate range (20%–80%), the closer it was to 40%–50% the mutant load, the wider the distribution. Mutant loads were found to be similar in amniocytes and cord blood cells, at variance with placenta samples. mtDNA content correlated to mutant load in m.3243A>G placentas only.Conclusion These data indicate that (1) mutant load determined from CVS has to be interpreted with caution for PND of some mtDNA disorders and should be associated with/substituted by a mutant load measurement on amniocytes; (2) the m.3243A>G mutation behaves differently from other mtDNA mutations with respect to the impact on mtDNA copy number, as previously shown in human preimplantation embryogenesis.