Live birth derived from oocyte spindle transfer to prevent mitochondrial disease

Abstract Mutations in mitochondrial DNA (mtDNA) are maternally inherited and can cause fatal or debilitating mitochondrial disorders. The severity of clinical symptoms is often associated with the level of mtDNA mutation load or degree of heteroplasmy. Current clinical options to prevent transmissio...

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Bibliographic Details
Published in:Reproductive biomedicine online 2017-04, Vol.34 (4), p.361-368
Main Authors: Zhang, John, Liu, Hui, Luo, Shiyu, Lu, Zhuo, Chávez-Badiola, Alejandro, Liu, Zitao, Yang, Mingxue, Merhi, Zaher, Silber, Sherman J, Munné, Santiago, Konstandinidis, Michalis, Wells, Dagan, Huang, Taosheng
Format: Article
Language:English
Subjects:
Cytoplasm
DNA, Mitochondrial - chemistry
Female
Fertilization in Vitro
Heterozygote
Humans
Leigh Disease - genetics
Leigh Disease - prevention & control
Leigh syndrome
Live Birth
Maternal Inheritance
Meiotic spindle
Mitochondria
Mitochondrial Replacement Therapy
Nuclear transfer
Obstetrics and Gynecology
Oocyte
Oocyte Donation
Oocytes - ultrastructure
Pedigree
Pregnancy
Preimplantation Diagnosis
Sequence Analysis, DNA
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Summary:Abstract Mutations in mitochondrial DNA (mtDNA) are maternally inherited and can cause fatal or debilitating mitochondrial disorders. The severity of clinical symptoms is often associated with the level of mtDNA mutation load or degree of heteroplasmy. Current clinical options to prevent transmission of mtDNA mutations to offspring are limited. Experimental spindle transfer in metaphase II oocytes, also called mitochondrial replacement therapy, is a novel technology for preventing mtDNA transmission from oocytes to pre-implantation embryos. Here, we report a female carrier of Leigh syndrome (mtDNA mutation 8993T > G), with a long history of multiple undiagnosed pregnancy losses and deaths of offspring as a result of this disease, who underwent IVF after reconstitution of her oocytes by spindle transfer into the cytoplasm of enucleated donor oocytes. A male euploid blastocyst wasobtained from the reconstituted oocytes, which had only a 5.7% mtDNA mutation load. Transfer of the embryo resulted in a pregnancy with delivery of a boy with neonatal mtDNA mutation load of 2.36–9.23% in his tested tissues. The boy is currently healthy at 7 months of age, although long-term follow-up of the child's longitudinal development remains crucial.
ISSN:1472-6483
1472-6491
DOI:10.1016/j.rbmo.2017.01.013