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Preimplantation genetic diagnosis for a carrier with m.3697G > A mitochondrial DNA mutation

  • Genetics
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Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Objective

To explore inheritance of the m.3697G > A mitochondrial DNA (mtDNA) mutation and the effectiveness of preimplantation genetic diagnosis (PGD) for the carrier.

Methods

The study encompassed a pedigree of m.3697G > A mtDNA mutation, including one asymptomatic patient who pursued for PGD treatment. Twelve cumulus oocyte complexes (COCs) were collected in the first PGD cycle and 11 COCs in the second cycle. The efficiency of cumulus cells, polar bodies, and trophectoderm (TE) in predicting the m.3697G > A heteroplasmy of embryos was analyzed.

Results

From 23 COCs, 20 oocytes were fertilized successfully. On day 5 and 6 post-fertilization, 15 blastocysts were biopsied. The m.3697G > A mutation load of TE biopsies ranged from 15.2 to 100%. In the first cycle, a blastocyst with mutation load of 31.7% and chromosomal mosaicism was transferred, but failed to yield a clinical pregnancy. In the second cycle, a euploid blastocyst with mutation load of 53.9% was transferred, which gave rise to a clinical pregnancy. However, the pregnancy was terminated due to fetal cleft lip and palate. The mutation loads of different tissues (47.7 ± 1.8%) from the induced fetus were comparable to that of the biopsied TE and amniotic fluid cell (49.7%). The mutation load of neither cumulus cells (R2 = 0.02, p = 0.58) nor polar bodies (R2 = 0.33, p = 0.13) correlated with TE mutation load which was regarded as a gold standard.

Conclusions

The m.3697G > A mutation showed a random pattern of inheritance. PGD could be used to reduce the risk of inheritance of a high mutation load. Cumulus cells are not a suitable predictor of blastocyst mutation load.

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Funding

This study was supported by the National Natural Science Foundation of China (81871216, 81971455, U20A20350).

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Author notes

  1. Dongmei Ji and Xinyuan Li contributed equally to this work.

Authors and Affiliations

  1. Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230022, Anhui, China

    Dongmei Ji, Xinyuan Li, Dawei Chen, Weiwei Zou, Xiaohong Deng, Yu Cao, Zhiguo Zhang, Ping Zhou, Hongying Sha & Yunxia Cao

  2. NHC Key Laboratory of Study On Abnormal Gametes and Reproductive Tract (Anhui Medical University), No. 81 Meishan Road, Hefei, 230032, Anhui, China

    Dongmei Ji, Xinyuan Li, Dawei Chen, Weiwei Zou, Zhiguo Zhang, Ping Zhou & Yunxia Cao

  3. Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of China, No. 81 Meishan Road, Hefei, 230032, Anhui, China

    Dongmei Ji, Xinyuan Li, Zhiguo Zhang, Ping Zhou & Yunxia Cao

  4. Reproductive Medicine Center, No. 120 Wanshui Road, Shushan District, the First Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, China

    Dongmei Ji, Xinyuan Li, Jianxin Pan, Kai Zong, Dawei Chen, Jordan Lee Marley, Weiwei Zou, Xiaohong Deng, Yu Cao, Zhiguo Zhang, Ping Zhou, Hongying Sha & Yunxia Cao

  5. Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China

    Xinyuan Li

  6. State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Jianxin Pan & Hongying Sha

  7. China Technical Center of Hefei Customs District, No. 329 Tunxi Road, Hefei, 230022, Anhui, China

    Kai Zong

  8. Biosciences Institute, Tyne and Wear, Newcastle University,, Newcastle Upon Tyne, NE1 8PB, UK

    Jordan Lee Marley

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  1. Dongmei Ji
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  2. Xinyuan Li
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  3. Jianxin Pan
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Corresponding authors

Correspondence to Hongying Sha or Yunxia Cao.

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Ji, D., Li, X., Pan, J. et al. Preimplantation genetic diagnosis for a carrier with m.3697G > A mitochondrial DNA mutation. J Assist Reprod Genet 38, 3251–3260 (2021). https://doi.org/10.1007/s10815-021-02354-3

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  • DOI: https://doi.org/10.1007/s10815-021-02354-3

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