Zitao Liu, Hui Liu, Zhuo Lu, S. Luo, Alejandro Chavez, Mingxue Yang, Z. Merhi, S. Silber, S. Munné, M. Konstantinidis, D. Wells, Taosheng Huang, John Zhang
{"title":"Prevention of Mitochondrial Disease Caused by mtDNA Mutation through Mitochondrial Replacement Therapy (MRT)","authors":"Zitao Liu, Hui Liu, Zhuo Lu, S. Luo, Alejandro Chavez, Mingxue Yang, Z. Merhi, S. Silber, S. Munné, M. Konstantinidis, D. Wells, Taosheng Huang, John Zhang","doi":"10.18143/JWMS_V2I2_1971","DOIUrl":null,"url":null,"abstract":"Objective: We investigated the role of MRT in preventing mitochondrial diseases caused by mtDNA mutation. Method: MRT was conducted by spindle nuclear transfer (SNT) between human oocytes. Mutant mtDNA load was analyzed. Results: of 18 oocytes collected from a female carrier (24.5% mtDNA 8993T>G) of Leigh Syndrome, 7 oocytes (haplogroup I) were attempted for MRT to enucleated donor oocytes (haplogroup L2c). Of the 4 blastocysts created from the 5 reconstituted oocytes, 1 euploid embryo was achieved, carrying 5.73% mtDNA 8993T>G mutation load comparing to 3.66% in an aneuploid embryo. The calculated mtDNA 8993T>G load was about 100% in both carrier’s oocytes, from which the above two embryos were created. A boy was delivered after euploid embryo transfer to the carrier. The mutant mtDNA load was differentiated expressed among the fetal and fetal appendage tissues, ranging from 0% to 9.23%. The child is still asymptomatic of Leigh Syndrome or other diseases at 5-month old now. Conclusions: Mitochondrial disease caused by mtDNA mutation may be prevented by MTR through SNT among different haplogroups. More cases and a long term follow-up are warranted to evaluate the safety of this technique.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"4 1","pages":"0"},"PeriodicalIF":0.0000,"publicationDate":"2016-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of World Mitochondria Society","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.18143/JWMS_V2I2_1971","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: We investigated the role of MRT in preventing mitochondrial diseases caused by mtDNA mutation. Method: MRT was conducted by spindle nuclear transfer (SNT) between human oocytes. Mutant mtDNA load was analyzed. Results: of 18 oocytes collected from a female carrier (24.5% mtDNA 8993T>G) of Leigh Syndrome, 7 oocytes (haplogroup I) were attempted for MRT to enucleated donor oocytes (haplogroup L2c). Of the 4 blastocysts created from the 5 reconstituted oocytes, 1 euploid embryo was achieved, carrying 5.73% mtDNA 8993T>G mutation load comparing to 3.66% in an aneuploid embryo. The calculated mtDNA 8993T>G load was about 100% in both carrier’s oocytes, from which the above two embryos were created. A boy was delivered after euploid embryo transfer to the carrier. The mutant mtDNA load was differentiated expressed among the fetal and fetal appendage tissues, ranging from 0% to 9.23%. The child is still asymptomatic of Leigh Syndrome or other diseases at 5-month old now. Conclusions: Mitochondrial disease caused by mtDNA mutation may be prevented by MTR through SNT among different haplogroups. More cases and a long term follow-up are warranted to evaluate the safety of this technique.