Abstract
Purpose
To identify the disease-causing gene in a family with female infertility and fertilization failure.
Methods
Whole-exome sequencing and Sanger sequencing were used to identify the disease-causing gene in a female with infertility and fertilization failure. Subcellular localization and western blot analysis were used to check the effect of mutations.
Results
We identified novel compound heterozygous mutations c.598C>T (p.Arg200Ter) and c.1319G>C (p.Trp440Ser) in WEE2 gene in a female with infertility and fertilization failure. The p.Arg200Ter mutant WEE2 gene produce truncated protein and mainly located in the nucleus, the same as the wild protein, while the p.Trp440Ser mutant WEE2 proteins are located in the nucleus and cytoplasm and the expression level of p.Trp440Ser mutant WEE2 protein is reduced significantly compared with that of wild-type WEE2.
Conclusions
We discovered novel compound heterozygous mutations c.598C>T (p.Arg200Ter) and c.1319G>C (p.Trp440Ser) in WEE2 gene in a female whose oocytes could not form pronucleus after intracytoplasmic sperm injection (ICSI). Moreover, mutations in WEE2 gene affect the normal function of WEE2 proteins and cause fertilization failure.
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Acknowledgments
We thank Lei Wang and Qing Sang in Fudan University for their gift of WEE2 plasmid and the family members for their enthusiastic participation in this study.
Funding
This work was supported by grants from the National Natural Science Foundation of China (81000079, 81170165, 81870959 to X.Z.) and supported by Program for HUST Academic Frontier Youth Team.
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This study was approved by the ethics committee of Huazhong University of Science and Technology. All participants in the study agreed with informed consent to participate in the investigation.
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Zhou, X., Zhu, L., Hou, M. et al. Novel compound heterozygous mutations in WEE2 causes female infertility and fertilization failure. J Assist Reprod Genet 36, 1957–1962 (2019). https://doi.org/10.1007/s10815-019-01553-3
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DOI: https://doi.org/10.1007/s10815-019-01553-3