Abstract
Peptidyl arginine deiminase, type VI (PADI6) is a member of the subcortical maternal complex (SCMC), which plays vital roles in mammalian embryogenesis. Most mutations in SCMC members have been reported to cause human embryonic arrest, and a total of 15 mutations in PADI6 have been shown to be responsible for early embryonic arrest according to previous studies. However, the genetic factors behind this phenotype remain to be understood in further detail. Here, we identified 13 novel mutations and 4 previously reported mutations of PADI6 in 14 patients who were diagnosed with abnormal embryonic development caused by early arrest, embryonic fragmentation, and recurrent implantation failure. Most of the mutations were predicted by in silico analysis to be deleterious or damaging to the function of PADI6. In addition, the total and East Asian population frequencies of the mutations were low or absent in the gnomAD database. Our study expands the mutational spectrum in PADI6 and will provide precise targets for genetic counseling in the future.
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Acknowledgements
The authors thank the patients and their families for participating in this study, as well as the doctors for collecting samples and providing clinical support.
Funding
This work was supported by the National Natural Science Foundation of China (81725006, 81822019, 81771581, 81771649, 81971450, 81971382, 82001538, 82071642 and 81901561), the project supported by the Shanghai Municipal Science and Technology Major Project (2017SHZDZX01), the Project of the Shanghai Municipal Science and Technology Commission (19JC1411001), the Natural Science Foundation of Shanghai (19ZR1444500, 21ZR1404800), the Shuguang Program of the Shanghai Education Development Foundation and the Shanghai Municipal Education Commission (18SG03), the Foundation of the Shanghai Health and Family Planning Commission (20154Y0162), 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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QingS, LW, and JD conceived and designed the research study. JF, ZY, LL, QiuwenS, RS, FD, and YQ collected the clinical samples. BC organized the medical records and analyzed the whole-exome data. JD, YZ, and RL performed the genome sequencing. QingS and JD drafted and revised the manuscript.
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The authors declare no competing interests.
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Our study was approved by the Ethics Committee of the Medical College of Fudan University and the Reproductive Study Ethics Committees of the hospital. All blood samples were donated for the investigation after informed consent.
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Dong, J., Fu, J., Yan, Z. et al. Novel biallelic mutations in PADI6 in patients with early embryonic arrest. J Hum Genet 67, 285–293 (2022). https://doi.org/10.1038/s10038-021-00998-8
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DOI: https://doi.org/10.1038/s10038-021-00998-8
