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Live births following preimplantation genetic testing for dynamic mutation diseases by karyomapping: a report of three cases

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

Abstract

Purpose

The preimplantation genetic testing for monogenic defects (PGT-M) is a beneficial strategy for the patients suffering from a Mendelian disease, which could protect their offspring from inheriting the disease. The purpose of this study is to report the effectiveness of PGT-M based on karyomapping for three cases of dynamic mutation diseases with trinucleotide repeat expansion.

Methods

PGT-M was carried out on three couples, whose family members were diagnosed with Huntington’s disease or spinocerebellar ataxias 2 or 12. The whole genome amplification was obtained using the multiple displacement amplification (MDA) method. Then, karyomapping was performed to detect the allele that is carrying the trinucleotide repeat expansion using single nucleotide polymorphism (SNP) linkage analyses, and the copy number variations (CNVs) of the embryos were also identified. Prenatal diagnosis was performed to validate the accuracy of PGT-M.

Results

PGT-M was successfully performed on the three couples, and they accepted the transfers of euploid blastocysts without the relevant pathogenic allele. The clinical pregnancies were acquired and the prenatal diagnosis of the three families confirmed the effectiveness of karyomapping. The three born babies were healthy and free of the pathogenic alleles HTT, ATXN2, or PPP2R2B corresponding to Huntington’s disease, spinocerebellar ataxias 2 or 12, respectively.

Conclusion

This study shows that karyomapping is a highly powerful and efficient approach for dynamic mutation detection in preimplantation embryos. In this work, we first report the birth of healthy babies that are free of the pathogenic gene for dynamic mutation diseases in patients receiving PGT-M by karyomapping.

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Acknowledgments

We thank the families for taking part and everybody involved in the research for their contributions.

Funding

This work was supported by National Key R&D Program of China (2019YFA0110900 to Yingpu Sun and Jiawei Xu, and 2019YFA0802200 to Jiawei Xu), National Natural Science Foundation of China (31870817 to Jiawei Xu.), Scientific and Technological Innovation Talent Project of Universities of Henan Province (20HASTIT045 to Jiawei Xu), and Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center (to Yingpu Sun and Jiawei Xu).

Author information

Author notes

  1. Dayuan Shi and Jiawei Xu contributed equally to this work.

Authors and Affiliations

  1. Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Dayuan Shi, Jiawei Xu, Wenbin Niu, Yidong Liu, Hao Shi, Guidong Yao, Senlin Shi, Gang Li, Wenyan Song, Haixia Jin & Yingpu Sun

  2. Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Dayuan Shi, Jiawei Xu, Wenbin Niu, Yidong Liu, Hao Shi, Guidong Yao, Senlin Shi, Gang Li, Wenyan Song, Haixia Jin & Yingpu Sun

  3. Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Dayuan Shi, Jiawei Xu, Wenbin Niu, Yidong Liu, Hao Shi, Guidong Yao, Senlin Shi, Gang Li, Wenyan Song, Haixia Jin & Yingpu Sun

  4. Henan Engineering Laboratory of Preimplantation Genetic Diagnosis and Screening, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Dayuan Shi, Jiawei Xu, Wenbin Niu, Yidong Liu, Hao Shi, Guidong Yao, Senlin Shi, Gang Li, Wenyan Song, Haixia Jin & Yingpu Sun

Authors
  1. Dayuan Shi
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  11. Yingpu Sun
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Contributions

Y.S. and J.X designed the study; G.Y., S.S., W.S., and H.J. performed embryo culture and biopsy; H.S. and G.L. collected the data; W.N., Y.L., and D.S. analyzed the data; D.S. drafted the manuscript; and J.X. revised it.

Corresponding authors

Correspondence to Jiawei Xu or Yingpu Sun.

Ethics declarations

All couples signed informed consent forms for ICSI treatment, PGT, cryopreservation, thawing, and transfer of embryos. The protocols for this study were evaluated and approved by the Internal Review Board of The First Affiliated Hospital of Zhengzhou University.

Conflict of interest

The authors declare that they have no conflicts of interest.

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Electronic supplementary material

Supplemental Figure 1

Copy number variations (CNVs) of case 2 and case 3. The CNVs of case 2 are shown by the B-allele and Log R charts in a and b: a. Del(5)(pter-p13.1) in embryo E7; b. Transferred euploid embryo E3. The CNVs of case 3 are displayed in c-g: c. Del(22)(q13.1-q13.2) in embryo E1; d. 47, XXY in embryo E2; e. Monosomy of the 14th chromosome in embryo E4; f. Multiple trisomy of the chromosomes 2, 5, 10, 11, 14, 15 and 16 in embryo E5; g. Transferred euploid embryo E11. (PNG 3305 kb)

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Shi, D., Xu, J., Niu, W. et al. Live births following preimplantation genetic testing for dynamic mutation diseases by karyomapping: a report of three cases. J Assist Reprod Genet 37, 539–548 (2020). https://doi.org/10.1007/s10815-020-01718-5

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  • DOI: https://doi.org/10.1007/s10815-020-01718-5

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