Detection of Putative Novel Mutation in Zp1 Gene Causing Empty Follicle Syndrome

Abstract

Abstract Introduction/Objective Mutations in the zona pellucida glycoprotein genes have been reported to be associated with empty follicle syndrome (EFS) and abnormal zona pellucida (ZP). At our clinic, in a cohort of infertile patients, we found three cases with empty follicle syndrome as a root cause of infertility. Further, we designed a study to identify the disease-causing gene mutations in these patients. At present, there are no citations or functional evidence in ClinVar for NM_207341.3:c.1168del variant indicating the involvement of this variant in empty follicle syndrome. But it has been interpreted to be Likely pathogenic causing female infertility due to zona pellucida defect. Methods/Case Report In this prospective study conducted at Al Ain Fertility Center (AAFC), U.A.E, we performed genetic analysis on three patients (first-degree sisters) having a mean age of 31.7 (2.52) years. Patient indications were primary female infertility and IVF failures due to no eggs present in the follicles when egg retrieval was attempted. We characterized these three patients as suffering from empty follicle syndrome. Along with the patient's sample, we also included their common parent's sample for Whole Exome Sequencing and Sanger sequencing, to rule out the inheritance pattern in the family. The effects of this mutation were further characterized through mRNA and protein studies. Results (if a Case Study enter NA) N/A. Conclusion To our knowledge, this is the first study in the U.A.E. showing the familial novel variant in the ZP1 gene associated with empty follicle syndrome. We identified a novel mutation in these patients (NM_207341.3:c.1168del) in the ZP1 gene in the homozygous state and the same variant in the heterozygous state in the parents. Our findings add to the existing mutational spectrum of the ZP1 gene associated with empty follicle syndrome and abnormal oocytes and provide new support for the genetic diagnosis of female infertility.