近日，澳大利亚莫纳什大学Mary Herbert团队研究了线粒体捐献和植入前mtDNA疾病基因检测。这一研究成果于2025年7月16日发表在《新英格兰医学杂志》上。

携带线粒体DNA （mtDNA）致病性变异的妇女所生的孩子有患一系列临床综合征的风险，这些综合征统称为mtDNA病。原核移植的线粒体捐献包括将患病妇女的受精卵的核基因组移植到未受影响妇女捐赠的去核受精卵上。因此，原核移植为受影响的妇女提供了生育与遗传相关的孩子的可能性，并降低了患mtDNA疾病的风险。

研究组向一系列具有致病性mtDNA变异的妇女提供线粒体捐赠（通过原核移植）或植入前基因检测（PGT），这些妇女寻求减少这些变异传给子女的可能性。异质性患者（在一定比例的mtDNA拷贝中存在变异）接受PGT治疗，同源性患者（在所有mtDNA拷贝中存在变异）或异质性升高的患者接受原核移植。

:22例患者中有8例（36%）和39例患者中有16例（41%）分别因原核移植或PGT而接受卵胞浆内单精子注射手术。原核移植导致8例活产和1例妊娠。PGT导致18例活产。母亲接受原核移植的8名婴儿血液中的异质性水平从无法检测到到16%不等。6例新生儿的母体致病性mtDNA变异水平比相应的去核受精卵低95 ~ 100%，2例新生儿低77 ~ 88%。在母亲接受PGT治疗的18名婴儿中，有10名婴儿的异质性水平是已知的，从检测不到到7%不等。

研究结果表明，研究小组发现通过原核移植的线粒体捐赠与人类胚胎的生存能力是相容的。一个包括原核转移和PGT的综合项目有效地减少了同质和异质致病mtDNA变异的传播。

附：英文原文

Title: Mitochondrial Donation and Preimplantation Genetic Testing for mtDNA Disease

Author: Louise A. Hyslop, Emma L. Blakely, Magomet Aushev, Jordan Marley, Yuko Takeda, Angela Pyle, Eilis Moody, Catherine Feeney, Jan Dutton, Carol Shaw, Sarah J. Smith, Kate Craig, Charlotte L. Alston, Lisa Lister, Karina Endacott, Samantha Byerley, Helen McDermott, Kathryn Wilson, Lynne Botham, Beth Matthew, Nilendran Prathalingam, Matthew Prior, Alison Murdoch, Douglass M. Turnbull, Gavin Hudson, Meenakshi Choudhary, Robert W. Taylor, Rekha N. Pillai, Jane A. Stewart, Robert McFarland, Mary Herbert

Issue&Volume: 2025-07-16

Abstract:

Background

Children born to women who carry pathogenic variants in mitochondrial DNA (mtDNA) are at risk for a range of clinical syndromes collectively known as mtDNA disease. Mitochondrial donation by pronuclear transfer involves transplantation of nuclear genome from a fertilized egg from the affected woman to an enucleated fertilized egg donated by an unaffected woman. Thus, pronuclear transfer offers affected women the potential to have a genetically related child with a reduced risk of mtDNA disease.

Methods

We offered mitochondrial donation (by pronuclear transfer) or preimplantation genetic testing (PGT) to a series of women with pathogenic mtDNA variants who sought to reduce the transmission of these variants to their children. Patients with heteroplasmy (variants present in a proportion of copies of mtDNA) were offered PGT, and patients with homoplasmy (variants present in all copies of mtDNA) or elevated heteroplasmy were offered pronuclear transfer.

Results

Clinical pregnancies were confirmed in 8 of 22 patients (36%) and 16 of 39 patients (41%) who underwent an intracytoplasmic sperm injection procedure for pronuclear transfer or for PGT, respectively. Pronuclear transfer resulted in 8 live births and 1 ongoing pregnancy. PGT resulted in 18 live births. Heteroplasmy levels in the blood of the 8 infants whose mothers underwent pronuclear transfer ranged from undetectable to 16%. Levels of the maternal pathogenic mtDNA variant were 95 to 100% lower in 6 newborns and 77 to 88% lower in 2 newborns than in the corresponding enucleated zygotes. Heteroplasmy levels were known for 10 of the 18 infants whose mothers underwent PGT and ranged from undetectable to 7%.

Conclusions

We found that mitochondrial donation through pronuclear transfer was compatible with human embryo viability. An integrated program involving pronuclear transfer and PGT was effective in reducing the transmission of homoplasmic and heteroplasmic pathogenic mtDNA variants.

DOI: NJ202507160000001

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2415539