A novel homozygous nonsense ZP1 variant causes human female infertility associated with empty follicle syndrome (EFS)

Abstract

Abstract Background Empty follicle syndrome (EFS) is a rare but severe condition in which no oocyte is recovered in female patients undergoing in vitro fertilization (IVF) after sufficient ovarian response to hormonal trigger. Accumulating evidence highlights the genetic basis of EFS occurrence. Methods In this study, we report a patient with primary infertility showing the characteristics of EFS from a consanguineous family. Under the treatment of assisted reproductive technique (ART), no oocyte was retrieved following the aspiration of mature follicles. Through whole‐exome sequencing (WES), we discovered a novel recessively transmitted mutation in ZP1 (c.769 C>T, p. Q257*). Results In vitro Co‐immunoprecipitation assays showed that mutant ZP1 protein failed to interact with either ZP2 or ZP3, which explains the degenerated oocytes in the patient with EFS. Conclusion Together, our data further expand the spectrum of ZP1 mutations that are associated with human EFS and thus provide novel insight into the diagnosis of EFS patients.

Keywords

• empty follicle syndrome (EFS)
• in vitro fertilization (IVF)
• whole‐exome sequencing (WES)
• zona pellucida (ZP)
• ZP1