Abstract
Purpose
We aimed to identify novel variants in TUBB8 and corresponding new abnormal phenotypes in oocytes/fertilization/ embryonic development responsible for female infertility.
Methods
Sanger sequencing of TUBB8 was performed in infertile women with abnormalities in oocyte maturation or embryonic development. The effects of the variants were evaluated in patients’ oocytes by morphological observations and immunofluorescence.
Results
We identified 34 novel variants of TUBB8 in 51 patients who were diagnosed with abnormalities in oocyte maturation or early embryonic development. We found a novel phenotype in which large polar bodies were present in three independent patients possibly associated with a recurrent variant. Moreover, we identified a novel type of TUBB8 variant consisting of an in-frame deletion-insertion, which has not been previously reported.
Conclusions
Our present study identified 34 novel variants in TUBB8 in 51 patients. These patients show oocyte maturation arrest, oocytes with large polar body, fertilization failure, early embryonic arrest or embryonic implantation failure. These results expand the kinds of variants and phenotypic spectrum of TUBB8 variants with regard to female infertility.
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Acknowledgments
We thank the patients and their families for participating in this study, as well as the doctors for contributing to patient sample collection and for providing clinical support. We also thank Ke Qiao from the core facility of the Institute of Metabolic & Integrative Biology, Fudan University, for her excellent technical expertise in cell imaging techniques.
Funding
This work was supported by the National Key Research and Development Program of China (2018YFC1003800, 2016YFC1000600, 2017YFC1001500), the National Natural Science Foundation of China (81725006, 81822019, 81771581, 81971450, 81771649 and 81971382), the project supported by Shanghai Municipal Science and Technology Major Project (2017SHZDZX01), the Project of Shanghai Municipal Science and Technology Commission(19JC1411001), the Shanghai Rising Star Program (17QA1400200), the Natural Science Foundation of Shanghai (19ZR1444500, 17ZR1401900), Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission (18SG03), the capacity Building Planning Program for Shanghai Women and Children’s Health Service, and the collaborative innovation center project construction for Shanghai women and children’s health
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YG, SX, Ling W, ZY, BL, JF, RS, JS, XS and YK contributed to the recruitment, characterization, and oocyte imaging of the patients. LZ, QS, and Lei W conceived and designed the research study. LZ and WW performed the exon sequencing, and LZ performed the immunostaining. BC, JM, Jie D, and QL organized the medical records. Zhihua Z, Zhou Z, and Jing D analyzed the data. LZ, QS, and Lei W wrote the initial draft of the manuscript. LJ and LH helped in improving the manuscript.
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This study was approved by the ethics committee of the Ninth Hospital of Shanghai Jiao Tong University and the institutional review board of the Medical College of Fudan University.
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Zhao, L., Guan, Y., Wang, W. et al. Identification novel mutations in TUBB8 in female infertility and a novel phenotype of large polar body in oocytes with TUBB8 mutations. J Assist Reprod Genet 37, 1837–1847 (2020). https://doi.org/10.1007/s10815-020-01830-6
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DOI: https://doi.org/10.1007/s10815-020-01830-6