Abstract
Purpose
This study aims to identify the genetic causes of 12 women with primary infertility characterized by primarily oocyte maturation abnormality and consequent early embryonic arrest.
Methods
Genomic DNA was isolated from peripheral blood samples. Whole-exome sequencing was performed on the probands, and the identified variants were confirmed by Sanger sequencing. The pathogenicity of the identified variants on the protein was accessed in silico. And we used qRT-PCR to detect the possible effects of the novel mutation on the mRNA level of NLRP5.
Results
A novel homozygous frameshift variant (p.V429Efs*30) in NLRP5 and compound heterozygous variants with a novel frameshift variant (p.A297Efs*20) and a recurrent variant (c. 223-14_223-2delCCCTCCTGTTCCA) in PATL2 were identified in two unrelated affected individuals. qRT-PCR showed an obvious decrease of the mutant NLRP5 mRNA. In addition, the truncated proteins of NLRP5 and PATL2 were predicted to be non-functional due to the deletion of the most or the whole region of the critical functional domain(s) respectively.
Conclusions
This study identified novel mutations in NLRP5 and PATL2, further expanding the mutational and phenotypic spectrum of both genes. This is the first report of the NLRP5 mutations that associates with oocyte maturation abnormality in humans.
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Acknowledgements
We thank all families for participating in this study.
Funding
This study was supported by the National Natural Science Foundation of China (81801440 to L.H.), the Natural Science Foundation of Anhui Province (1808085MH241 to L.H.), the Fundamental Research Funds for the Central Universities (WK9110000028 to L.H.), and the National Key R&D Program of China (2018YFC1003900 to X.T.).
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L.H., R.J., and X.T. conceived and designed the experiments. L.H., F.L., Q.J, J.J., L.L., R.J., and X.T. collected the samples. L.H. and Y.W. performed the experiments. L.H., Y.W., and G.S. analyzed the data. L.H. wrote the paper. All authors approved the final manuscript.
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The study was approved by the biomedical research ethics committee of the University of Science and Technology of China.
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Huang, L., Wang, Y., Lu, F. et al. Novel mutations in NLRP5 and PATL2 cause female infertility characterized by primarily oocyte maturation abnormality and consequent early embryonic arrest. J Assist Reprod Genet 39, 711–718 (2022). https://doi.org/10.1007/s10815-022-02412-4
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DOI: https://doi.org/10.1007/s10815-022-02412-4