Novel biallelic mutations in PADI6 in patients with early embryonic arrest

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.

Automated summary

This study identified 13 novel mutations and 4 previously reported mutations of PADI6 in 14 patients diagnosed with abnormal embryonic development caused by early arrest, embryonic fragmentation, and recurrent implantation failure. In silico analysis predicted that most of the mutations were deleterious or damaging to the function of PADI6. Furthermore, these mutations had low or absent frequencies in the gnomAD database, particularly in the East Asian population. The findings expand the mutational spectrum in PADI6 and have implications for genetic counseling in the future.