Live birth derived from oocyte spindle transfer to prevent mitochondrial disease
Live birth derived from oocyte spindle transfer to prevent mitochondrial disease
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DOI：
10.1016/j.rbmo.2017.01.013
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发表时间：
2017-04-01
影响因子：
4
通讯作者：
Huang, Taosheng
中科院分区：
文献类型：
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作者：
Zhang, John;Liu, Hui;Huang, Taosheng
线粒体DNA（mtDNA）突变是母系遗传的，可能导致致命或使人衰弱的线粒体疾病。临床症状的严重程度通常与mtDNA突变负荷水平或异质性程度相关。目前，防止mtDNA突变传播给后代的临床选择有限。实验性纺锤体移植（又称线粒体替代疗法）是一种阻止线粒体DNA从卵母细胞向植入前胚胎转移的新技术。在这里，我们报告了一位Leigh综合征（mtDNA突变8993 T> G）的女性携带者，由于这种疾病，她有多次未确诊的妊娠丢失和后代死亡的长期病史，她通过纺锤体转移到去核供体卵母细胞的细胞质中重建卵母细胞后接受了IVF。从重构的卵母细胞中获得雄性整倍体囊胚，其仅具有5.7%的mtDNA突变负荷。胚胎移植导致妊娠，分娩一名男孩，其检测组织中新生儿mtDNA突变负荷为2.36-9.23%。该男孩目前在7个月大时是健康的，尽管对该儿童的纵向发育进行长期随访仍然至关重要。(C)2017生殖保健有限公司由爱思唯尔有限公司出版。版权所有。
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 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 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. (C) 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.