Live birth derived from oocyte spindle transfer to prevent mitochondrial disease
John Z. H. Zhang,Hui Liu,Shiyu Luo,Zhuo Lu,Alejandro Chavez-Badiola,Zitao Liu,Mingxue Yang,Zaher Merhi,Sherman J. Silber,Santiago Munné,M. Konstantinidis,Dagan Wells,Jian J. Tang,Taosheng Huang +13 more
Reads0
Chats0
TLDR
A female carrier of Leigh syndrome, 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 is reported.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.read more
Citations
More filters
Journal ArticleDOI
Biparental Inheritance of Mitochondrial DNA in Humans.
Shiyu Luo,C. Alexander Valencia,Jinglan Zhang,Ni-Chung Lee,Jesse Slone,Baoheng Gui,Xinjian Wang,Zhuo Li,Sarah Dell,Jenice Brown,Stella Chen,Yin-Hsiu Chien,Wuh-Liang Hwu,Pi-Chuan Fan,Lee-Jun C. Wong,Paldeep S. Atwal,Taosheng Huang +16 more
TL;DR: The results suggest that, although the central dogma of maternal inheritance of mtDNA remains valid, there are some exceptional cases where paternal mtDNA could be passed to the offspring and may even lead to the development of new avenues for the therapeutic treatment for pathogenic mtDNA transmission.
Journal ArticleDOI
Mitochondrial Diseases: Hope for the Future
TL;DR: This review focuses on the latest advances in the development of treatments for mitochondrial disease, both small molecules and gene therapies, as well as methods to prevent transmission of mitochondrial disease through the germline.
Journal ArticleDOI
Mitochondrial genetic medicine.
TL;DR: Because mtDNA is maternally inherited and cytoplasmic, it has fostered the first germline gene therapy, nuclear transplantation, and effective interventions are still lacking for existing patients with mitochondrial dysfunction.
Journal ArticleDOI
Mitochondrial medicine in the omics era.
TL;DR: This Review aims to discuss recent advances in mitochondrial biology and medicine arising from widespread use of high-throughput omics technologies, and also includes a broad discussion of emerging therapies for mitochondrial disease.
Clinical application of pronuclear transfer to prevent mitochondrial DNA disease
TL;DR: In this article, pronuclear transplantation was used to reduce mtDNA carryover to <2% in the majority (79%) of PNT blastocysts, with no detectable effect on aneuploidy or gene expression.
References
More filters
Journal ArticleDOI
BLAT—The BLAST-Like Alignment Tool
TL;DR: How BLAT was optimized is described, which is more accurate and 500 times faster than popular existing tools for mRNA/DNA alignments and 50 times faster for protein alignments at sensitivity settings typically used when comparing vertebrate sequences.
Journal Article
A new mitochondrial disease associated with mitochondrial DNA heteroplasmy
TL;DR: A variable combination of developmental delay, retinitis pigmentosa, dementia, seizures, ataxia, proximal neurogenic muscle weakness, and sensory neuropathy occurred in four members of a family and was maternally transmitted as discussed by the authors.
Journal ArticleDOI
An estimation of the number of cells in the human body
Eva Bianconi,Allison Piovesan,Federica Facchin,Alina Beraudi,Raffaella Casadei,Flavia Frabetti,Lorenza Vitale,Maria Chiara Pelleri,Simone Tassani,Francesco Piva,Soledad Perez-Amodio,Pierluigi Strippoli,Silvia Canaider +12 more
TL;DR: Knowing the total cell number of the human body as well as of individual organs is important from a cultural, biological, medical and comparative modelling point of view.
Journal ArticleDOI
Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease.
Grainne S. Gorman,Andrew M. Schaefer,Yi Ng,Nicholas Gomez,Emma L. Blakely,Charlotte L. Alston,Catherine Feeney,Rita Horvath,Patrick Yu-Wai-Man,Patrick F. Chinnery,Robert W. Taylor,Douglass M. Turnbull,Robert McFarland +12 more
TL;DR: In this paper, the authors evaluated the minimum prevalence of symptomatic nuclear DNA mutations and symptomatic and asymptomatic mtDNA mutations causing mitochondrial diseases, and found that the mtDNA mutation rate was 1 in 5,000 (20 per 100,000), comparable with the previously published prevalence rates.
Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease. Annals of Neurology 2015, 77(5), 753-759.
TL;DR: This work comprehensively assessed the prevalence of all forms of adult mitochondrial disease to include pathogenic mutations in both nuclear and mtDNA.
Related Papers (5)
Mitochondrial replacement in human oocytes carrying pathogenic mitochondrial DNA mutations
Eunju Kang,Eunju Kang,Jun Wu,Nuria Marti Gutierrez,Amy Koski,Rebecca Tippner-Hedges,Karen Agaronyan,Aida Platero-Luengo,Paloma Martinez-Redondo,Hong Ma,Hong Ma,Yeon-Mi Lee,Tomonari Hayama,Crystal Van Dyken,Xinjian Wang,Shiyu Luo,Riffat Ahmed,Ying Li,Dongmei Ji,Dongmei Ji,Refik Kayali,Cengiz Cinnioglu,Susan B. Olson,Jeffrey T. Jensen,David Battaglia,David M. Lee,Diana Wu,Taosheng Huang,Don P. Wolf,Dmitry Temiakov,Juan Carlos Izpisua Belmonte,Paula Amato,Shoukhrat Mitalipov +32 more
Towards germline gene therapy of inherited mitochondrial diseases
Masahito Tachibana,Paula Amato,Michelle Sparman,Joy Woodward,Dario Melguizo Sanchis,Hong Ma,Nuria Marti Gutierrez,Rebecca Tippner-Hedges,Eunju Kang,Hyo Sang Lee,Cathy Ramsey,Keith Masterson,David Battaglia,David M. Lee,Diana Wu,Jeffrey T. Jensen,Jeffrey T. Jensen,Phillip E. Patton,Sumita Gokhale,Richard L. Stouffer,Richard L. Stouffer,Shoukhrat Mitalipov,Shoukhrat Mitalipov +22 more