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Novel mutation in the ZP1 gene and clinical implications

  • Genetics
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Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Empty follicle syndrome (EFS) is a complex reproductive disorder characterized by the repeated failure to aspirate oocytes from mature ovarian follicles during in vitro fertilization (IVF). In addition to some cases caused by iatrogenic problems and known genetic factors, there are still many unexplained aspects of EFS. Here, we aimed to assess the clinical and genetic characteristics of two EFS patients.

Methods

We have characterized two primary infertility patients with EFS in a nonconsanguineous family from China. Both the patients presented similar clinical phenotypes, that is a few granulosa cells but no oocytes could be retrieved during repeated cycles with normal follicular development, E2 levels, and bioavailable hCG plasma levels. Abnormal oocytes were obtained once or twice between multiple IVF cycles. We performed Sanger sequencing of the LHCGR and ZP1~ZP4 genes in the patients, and further bioinformatics analysis was performed to identify pathogenic elements in the genes.

Results

A novel mutation, c.181C>T (p.Arg61Cys), and a known mutation, c.1169_1176delTTTTCCCA (p.Ile390Thrfs*16), in the ZP1 gene were both identified in patient 2, but no mutations were identified in patient 1. The novel mutation inherited from her mother was absent in the control cohort and the ExAc database. The arginine residue is conserved at this position, and its replacement by cysteine was predicted to be deleterious. In another allele, a paternal frameshift mutation was predicted to introduce premature stop codons, resulting in the deletion of 234 amino acids from the C-terminus of the ZP1 protein.

Conclusions

Our findings presented compound heterozygous mutations in ZP1 associated with EFS and abnormal oocytes and provided further new evidence for the genetic basis of EFS and support for the genetic diagnosis of infertile individuals.

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Acknowledgments

The authors thank the patients and the control subjects for their participation in this study.

Funding

This work was partially supported by the National Natural Science Foundation of China (No. 81801431).

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Correspondence to Wenjun Wang.

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The authors declare that they have no conflicts of interest.

Ethics approval and consent to participate

The study protocol and all subjects who participated in this study were approved by the Institutional Review Board of our institute, and informed consent was obtained from all patients prior to their participation in accordance with institutional and national guidelines.

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Yuan, P., Li, R., Li, D. et al. Novel mutation in the ZP1 gene and clinical implications. J Assist Reprod Genet 36, 741–747 (2019). https://doi.org/10.1007/s10815-019-01404-1

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  • DOI: https://doi.org/10.1007/s10815-019-01404-1

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