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Complex preimplantation genetic tests for Robertsonian translocation, HLA, and X-linked hyper IgM syndrome caused by a novel mutation of CD40LG gene

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

Abstract

Purpose

To perform complex preimplantation genetic tests (PGT) for aneuploidy screening, Robertsonian translocation, HLA-matching, and X-linked hyper IgM syndrome (XHIGM) caused by a novel mutation c.156 G>T of CD40LG gene.

Methods

Reverse transcription PCR (RT-PCR) and Sanger sequencing were carried out to confirm the causative variant of CD40LG gene in the proband and parents. Day 5 and D6 blastocysts, obtained by in vitro fertilization (IVF) with intracytoplasmic sperm injection, underwent trophectoderm (TE) biopsy and whole genomic amplification (WGA) and next generation sequencing (NGS)-based PGT to detect the presence of a maternal CD40LG mutation, aneuploidy, Robertsonian translocation carrier, and human leukocyte antigen (HLA) haplotype.

Results

Sanger sequencing data of the genomic DNA showed that the proband has a hemizygous variant of c. 156 G>T in the CD40LG gene, while his mother has a heterozygous variant at the same position. Complementary DNA (cDNA) of CD40LG amplification and sequencing displayed that no cDNA of CD40LG was found in proband, while only wild-type cDNA of CD40LG was amplified in the mother. PGT results showed that only one of the six tested embryos is free of the variant c.156 G>T and aneuploidy and having the consistent HLA type as the proband. Meanwhile, the embryo is a Robertsonian translocation carrier. The embryo was transplanted into the mother’s uterus. Amniotic fluid testing results are consistent with that of PGT. A healthy baby girl was delivered, and the peripheral blood testing data was also consistent with the testing results of transplanted embryo.

Conclusions

The novel mutation of c. 156 G>T in CD40LG gene probably leads to XHIGM by nonsense-meditated mRNA decay (NMD), and complex PGT of preimplantation genetic testing for monogenic disease (PGT-M), aneuploidy (PGT-A), structural rearrangement (PGT-SR), and HLA-matching (PGT-HLA) can be performed in pedigree with both X-linked hyper IgM syndrome and Robertsonian translocation.

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Acknowledgments

We thank the family for their participation in this study.

Funding

The research was funded by the National Key Research and Development Program of China (2018YFC1003100, 2018YFC1004900), Natural Science Foundation of Shandong Province (ZR2018PH006, ZR2018MC014), and Key Research and Development Program of Shandong Province (2017G006035).

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Authors and Affiliations

  1. Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China

    Sexin Huang, Yuping Niu, Jie Li, Ming Gao, Junhao Yan, Shuiying Ma, Xuan Gao & Yuan Gao

  2. Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, 250012, Shandong, China

    Sexin Huang, Yuping Niu, Jie Li, Ming Gao, Junhao Yan, Shuiying Ma, Xuan Gao & Yuan Gao

  3. Shandong Key Laboratory of Reproductive Medicine, Jinan, 250012, Shandong, China

    Sexin Huang, Yuping Niu, Jie Li, Ming Gao, Junhao Yan, Shuiying Ma, Xuan Gao & Yuan Gao

  4. Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, 250012, Shandong, China

    Sexin Huang, Yuping Niu, Jie Li, Ming Gao, Junhao Yan, Shuiying Ma, Xuan Gao & Yuan Gao

  5. National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, 250012, Shandong, China

    Sexin Huang, Yuping Niu, Jie Li, Ming Gao, Junhao Yan, Shuiying Ma, Xuan Gao & Yuan Gao

  6. Shandong Provincial Hospital, Jinan, 250001, Shandong, China

    Yan Zhang

Authors
  1. Sexin Huang
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  2. Yuping Niu
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  3. Jie Li
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  4. Ming Gao
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  5. Yan Zhang
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  6. Junhao Yan
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  7. Shuiying Ma
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  8. Xuan Gao
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  9. Yuan Gao
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Corresponding author

Correspondence to Yuan Gao.

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The authors declare that they have no conflicts of interest.

Ethics approval

This project was approved by the Ethics Committee of the Reproductive Medical Hospital Affiliated to Shandong University.

Statement of informed consent

The couple signed informed consent forms for ICSI treatment and PGT.

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Cite this article

Huang, S., Niu, Y., Li, J. et al. Complex preimplantation genetic tests for Robertsonian translocation, HLA, and X-linked hyper IgM syndrome caused by a novel mutation of CD40LG gene. J Assist Reprod Genet 37, 2025–2031 (2020). https://doi.org/10.1007/s10815-020-01846-y

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  • DOI: https://doi.org/10.1007/s10815-020-01846-y

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