Novel variants in PADI6 genes cause female infertility due to early embryo arrest

Early embryo arrest is characterized by premature termination of development in preimplantation embryos. Human subcortical maternal complex (SCMC) is a protein complex that is specifically expressed in mammalian oocytes and early embryos and is essential for embryonic cell division. Peptidyl arginine deiminase 6 (PADI6) is proven to be a member of SCMC. Variants in the PADI6 gene have been shown to induce early embryo arrest. In this study, we performed genetic analysis in patients with female infertility due to early embryo arrest to identify the disease-causing gene variants.

Whole-exome sequencing and Sanger sequencing were used to identify the variants in the patients and their families. Western blotting and immunofluorescence staining were used to check the effects of the variants on expression and function of PADI6.

We identified a novel homozygous variant (c.358A > C [p.Thr120Pro]) and novel compound-heterozygous variants (c.2044C > T [p.Arg682Trp] and c.707dupT [p.Leu237Alafs*24]) in PADI6 in two infertile individuals with early embryo arrest. We found that these variants resulted in a decrease in the expression level of PADI6, which may lead to abnormal protein function. Immunofluorescence staining also suggested that these variants affected the expression of PADI6.

Our study expands the spectrum of genetic defects in female early embryo arrest and further supports the causality between PADI6 variants and female infertility.