Taosheng Huang, John Zhang, Hui Liu, Shiyu Luo, Zhuo Lu, Alejandro Chavez-Badiola, Zitao Liu, Mingxue Yang, Zaher Merhi, Sherman J Silber, Santiago Munne, Michalis Konstandinidis and Dagan Wells
Cincinnati Children's Hospital Medical Center, USA
New Hope Fertility Center, USA
NYU School of Medicine, USA
St. Luke's Hospital, USA
Reprogenetics LLC, USA
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 in heteroplasmy. Current clinical options to prevent transmission of mtDNA mutations to offspring are limited. Experimental nuclear transfer in metaphase II oocytes, also called mitochondrial replacement therapy, has been shown to be a novel technology in preventing mtDNA transmission from oocytes to pre-implantation embryos or pluripotent stem cells. Here, we report a female carrier of Leigh syndrome (24.5% of mtDNA 8993T>G mutation load), with a long history of multiple pregnancy losses and deaths of offspring due to this disease, underwent in vitro fertilization following reconstitution of her oocytes by spindle nuclear transfer into the cytoplasm of enucleated donor oocytes. A male euploid blastocyst was obtained 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 low mtDNA mutation load in all his tested tissues. The boy is currently healthy at seven months of age although long-term follow-up of the childā??s longitudinal development remains crucial.
Email: Taosheng.Huang@cchmc.org
