Information for genetic management of mtDNA disease: sampling pathogenic mtDNA mutants in the human germline and in placenta.

Journal of Medical Genetics
D MarchingtonJ Poulton

Abstract

Families with a child who died of severe, maternally inherited mitochondrial DNA (mtDNA) disease need information on recurrence risk. Estimating this risk is difficult because of (a) heteroplasmy-the coexistence of mutant and normal mtDNA in the same person-and (b) the so-called mitochondrial bottleneck, whereby the small number of mtDNAs that become the founders for the offspring cause variation in dose of mutant mtDNA. The timing of the bottleneck and of segregation of mtDNA during foetal life determines the management options. Therefore, mtDNA heteroplasmy was studied in oocytes and placenta of women in affected families. One mother of a child dying from Leigh syndrome due to the 9176T-->C mtDNA mutation transmitted various loads of mutant mtDNA to < or =3 of 20 oocytes. This was used to estimate recurrence as < or =5%. She subsequently conceived a healthy son naturally. Analysis of the placenta showed that some segregation also occurred during placental development, with the mutant mtDNA load varying by >10% in a placenta carrying 65% 3243A-->G mutant mtDNA. This is the first report of (a) an oocyte analysis for preconception counselling, specifically, refining recurrence risks of rare mutations and (b) a widely different l...Continue Reading

Citations

Aug 17, 2010·PLoS Genetics·Joanna PoultonIan J Holt
Mar 20, 2014·European Journal of Human Genetics : EJHG·Victoria NesbittRobert McFarland
Jan 29, 2013·Mitochondrial DNA·Marta CalatayudMaria Pilar Aluja
Oct 11, 2014·Molecular Human Reproduction·Luca GianaroliGiovanni Romeo
Sep 13, 2016·Neuromuscular Disorders : NMD·Yi Shiau NgRobert W Taylor
Jul 28, 2016·Journal of Medical Genetics·Suzanne C E H SalleveltHubert J M Smeets
Apr 19, 2017·Annual Review of Genomics and Human Genetics·Lyndsey CravenDoug M Turnbull
May 26, 2017·Molecular Diagnosis & Therapy·Joanna PoultonPatrick Yu-Wai-Man
Feb 20, 2021·Human Reproduction Open·Guido de WertUNKNOWN ESHRE Ethics Committee
Dec 15, 2010·Mitochondrion·Marcos Roberto ChiarattiJoanna Poulton

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