Abstract
Objective
A 32-year-old female was diagnosed with unexplained primary infertility for 10 years. She had roughly normal basal hormone levels, but her basal follicle-stimulating hormone (FSH) levels were elevated. In addition, the level of anti-Mullerian hormone was within the normal range, and she had undergone two failed oocyte collection attempts. We aimed to investigate the genetic cause of female infertility in patients with impaired ovarian folliculogenesis.
Methods
Genomic DNA was extracted from the peripheral blood of the patient and her family members. Whole-exome sequencing was performed on the patient, and TBPL2 mutations were identified and confirmed by Sanger sequencing. The Exome Aggregation Consortium (ExAC) Browser and Genome Aggregation Database (gnomAD) Browser Beta were used to search the allele frequencies of the variants in the general population. The harmfulness of the mutations was analyzed by SIFT, Mutation Taster, and CADD software.
Result
One novel mutation, c.802C > T (p. Arg268Ter), and one known variant, c.788 + 3A > G (p. Arg233Ter), in TBPL2 were identified in the infertile family. Compound heterozygous mutations in TBPL2 may be the cause of impaired ovarian folliculogenesis, failure of superovulation, and infertility.
Conclusions
We identified compound heterozygous mutations in TBPL2 that caused impaired ovarian folliculogenesis, failure of superovulation, and infertility in patients. These findings suggest an important role for compound heterozygous mutations in TBPL2 and expand the mutational spectrum of TBPL2, which might provide a new precise diagnostic marker for female infertility.
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Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Acknowledgements
We thank the family for participation in the study and the other members of Dr. Yao’s laboratory for their discussion and help.
Funding
This study was supported by grants from the National Nature Science Foundation of China (grant no. 81971373, 82274651, and grant no. 82001618), China Postdoctoral Science Foundation (Certificate Number: 2023M731413), and Jiangsu Funding Program for Excellent Postdoctoral Talent (NO: 2022ZB727).
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B. Y. and J. M. contributed to the conception and design of the study. T. D., M. L., and L. C. analyzed the data and drafted the manuscript. Y. S., Y. W., and H. W. participated in performing the experiments and were involved in data acquisition and analysis.
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Du, T., Li, M., Chen, L. et al. Compound heterozygous mutations in TBPL2 were identified in an infertile woman with impaired ovarian folliculogenesis. J Assist Reprod Genet 40, 2945–2950 (2023). https://doi.org/10.1007/s10815-023-02961-2
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DOI: https://doi.org/10.1007/s10815-023-02961-2