Abstract
Oocyte maturation arrest results in primary female infertility, but the genetic etiology of this phenotype remains largely unknown. Previously, we and other groups have reported that biallelic mutations in PATL2 are mainly responsible for human oocyte germinal vesicle-stage arrest and that the specific phenotype varies for different mutations. Here, we identified four novel missense mutations (p.V260M, p.Q300*, p.T425P, and p.D293Y), a novel frameshift mutation (p.N239Tfs*9), and a reported splicing mutation (p.R75Vfs*21) in PATL2 in seven affected individuals from five unrelated families, showing a multiplicity of phenotypes in oocyte maturation arrest, fertilization failure, or embryonic developmental arrest, which further expands the mutational and phenotypic spectrum in patients with PALTL2 mutations. This work further indicates the critical role of PATL2 in oocyte maturation and early embryo development and will provide a basis for pursuing the determination of genetic variation in PALT2 as an additional criterion for evaluating the quality of oocytes and embryos for assisted reproduction techniques.
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Acknowledgements
This research was supported by the National Natural Science Foundation of China (81771574, 81771649, 81300550, 81725006, 81822019, 81771581, and 81571501), the National Key Research and Development Program of China (2017YFC1001500, 2016YFC1000600, and 2018YFC1003800), the National Basic Research Program of China (2015CB943300), the Shanghai Municipal Commission of Health and Family Planning Foundation (20174Y0036), and the Shanghai Rising-Star Program 17QA1400200.
Author contributions
LW, BL and QS: literature review, collection of data, and drafting the manuscript; HC, DL, DS, BBC and ZY: data collection; QFL, LW, YPK, BL and QS: supervision of all aspects, including study design, data interpretation, and manuscript preparation.
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This study was approved by the ethics committee of Ninth Hospital affiliated with Shanghai Jiao Tong University (No. 20161206; approved on 5 December 2016). All immature oocytes were donated by affected individuals after they had provided written informed consent, and the control MII oocytes used in this study were matured in vitro from GV or MI oocytes.
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Wu, L., Chen, H., Li, D. et al. Novel mutations in PATL2: expanding the mutational spectrum and corresponding phenotypic variability associated with female infertility. J Hum Genet 64, 379–385 (2019). https://doi.org/10.1038/s10038-019-0568-6
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DOI: https://doi.org/10.1038/s10038-019-0568-6
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