A novel homozygous variant in PADI6 is associate with human cleavage-stage embryonic arrest

Guangyi Cao; Xiangyu Zhu; Yuling Lin; Junshun Fang; Xiaoyue Shen; Shanshan Wang; Na Kong

doi:10.3389/fgene.2023.1243230

A novel homozygous variant in PADI6 is associate with human cleavage-stage embryonic arrest

Front Genet. 2023 Aug 29:14:1243230. doi: 10.3389/fgene.2023.1243230. eCollection 2023.

Authors

Guangyi Cao^#^{1

2}, Xiangyu Zhu^#¹, Yuling Lin^#³, Junshun Fang^{1

2}, Xiaoyue Shen^{1

2}, Shanshan Wang^{1

2}, Na Kong^{1

2}

Affiliations

¹ Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
² Center for Molecular Reproductive Medicine, Nanjing University, Nanjing, China.
³ State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China.

^# Contributed equally.

Abstract

Repeated absence of useable embryos is a difficult problem for infertility patients. Among them, embryonic developmental arrest is more common, but the genetic cause is not known. The embryos of a patient who came to our hospital three times could not develop beyond the four-cell stage. In addition to recording the developmental details of the embryos by daily photo-taking, the PADI6 ^R132C homozygous variants was further confirmed by whole-exome sequencing. Subsequently, PADI6 ^R132C was analyzed by bioinformatics methods for conservativeness across species. In addition, the possible impact of the pathogenic mutation on the structure of the protein PADI6 were also assessed. Generally, we identified a homozygous variants [NM_207421.4, c.394C>T(p.R132C] in the middle protein-arginine deiminase domain in PADI6 gene. The homozygous variant is highly conserved across species. Homozygous variant in PADI6 ^R132C could cause a human cleavage-stage embryonic arrest in female patients. These findings provide further evidence for the important roles of the homozygous PADI6^R132C variant in embryonic development. Our findings contribute to a deeper understanding of the molecular genetic basis of female infertility.

Keywords: PADI6; cleavage arrest; embryos; mutation; reproduction.

Grants and funding

This work was supported by National Natural Science Foundation of China (32000563), Nanjing Health Science and Technology Development Special Fund Project (YKK20064), Nanjing Drum Tower Hospital Clinical Research Special fund cultivation project (2021-LCYJ-PY-08, 2023-LCYJ-PY-35), Fertility Research Program of Young and Middle-aged Physicians Basic Research project of Beijing Health Promotion Association (2022) and Startup Funds from Nanjing Drum Tower Hospital (RC2022-019).