Prevention of Mitochondrial Disease Caused by mtDNA Mutation through Mitochondrial Replacement Therapy (MRT)

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.
线粒体替代疗法(MRT)预防mtDNA突变引起的线粒体疾病
目的:探讨MRT在预防mtDNA突变引起的线粒体疾病中的作用。方法:采用人卵母细胞梭形核移植(SNT)进行核磁共振成像。分析突变体mtDNA负载。结果:从Leigh综合征女性携带者(24.5% mtDNA 8993T>G)收集的18个卵母细胞中,有7个卵母细胞(单倍群I)被尝试与去核供体卵母细胞(单倍群L2c)进行MRT。在5个重组卵母细胞形成的4个囊胚中,获得1个整倍体胚胎,携带5.73%的mtDNA 8993T>G突变负荷,而非整倍体胚胎携带3.66%的突变负荷。计算出的mtDNA 8993T>G在两名携带者的卵母细胞中的载量约为100%,由此产生了上述两个胚胎。在整倍体胚胎移植到携带者身上后,一名男孩出生了。突变体mtDNA载量在胎儿和胎儿附件组织中分化表达,范围为0% ~ 9.23%。该患儿目前5个月大仍无利氏综合征或其他疾病症状。结论:mtDNA突变引起的线粒体疾病可通过不同单倍群间的SNT进行MTR预防。需要更多的病例和长期随访来评估该技术的安全性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信