AUTHOR=Xu Yao , Wang Rongxiang , Pang Zhi , Wei Zhiyun , Sun Lihua , Li Sa , Wang Guanghua , Liu Yu , Zhou Yiwen , Ye Hongjuan , Jin Liping , Xue Songguo 

TITLE=Novel Homozygous PADI6 Variants in Infertile Females with Early Embryonic Arrest

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.819667

DOI=10.3389/fcell.2022.819667

ISSN=2296-634X

ABSTRACT=<p>Early embryonic arrest denotes premature termination of development in preimplantation embryos, which is one of the major phenotypes of recurrent assisted reproduction failure. Padi6 is proven to be a member of the subcortical maternal complex (SCMC) in mice, which is essential in oocyte maturation and embryogenesis. We and other groups previously found that biallelic mutations in <italic>PADI6</italic> caused female infertility manifesting as early embryonic arrest. In this study, we identified two novel homozygous variants (p.Cys163Arg, and p. Trp475*) of <italic>PADI6</italic> in two infertile patients from a cohort of 75 females with the phenotype of early embryonic arrest. An <italic>in vitro</italic> expression study indicated severe decrease of PADI6, which might destruct the stability of SCMC. Our study expands the mutational spectrum of <italic>PADI6</italic> and further supports the causality between <italic>PADI6</italic> mutations and female infertility.</p>