Primary infertility affects 15% of couples worldwide, yet many genetic causes remain unknown. Through whole‐exome sequencing of a woman with primary infertility and repeated embryo implantation failure, we identified a novel homozygous frameshift mutation in GREB1 (c.5364delC, p.Ala1789Argfs∗42). Sanger sequencing confirmed heterozygous carrier status in both parents. Functional studies demonstrated the absence of nonsense‐mediated mRNA decay but abnormal GREB1 protein expression via western blotting. Computational modeling predicted pathogenic structural alterations. This variant is absent in gnomAD/ExAC databases. Our findings establish GREB1 mutations as a novel cause of female infertility, highlighting its role in endometrial receptivity regulation.
Yang et al. (Thu,) studied this question.