Novel mutations in WEE2: Expanding the spectrum of mutations responsible for human fertilization failure

Abstract

Successful fertilization is fundamental for sexual reproduction. After undergoing a series of molecular and morphological changes, the haploid sperm fuses with the haploid oocyte to create a diploid zygote. Defects in this process might lead to human fertilization failure. We have previously found homozygous mutations in WEE2 that are responsible for human fertilization failure, but the genetic basis of human fertilization failure requires further investigation. In the present study, we screened for WEE2 mutations in a new cohort of patients with fertilization failure. Through Sanger sequencing of WEE2 exons, we identified seven novel mutations and two reported mutations in WEE2 from six affected individuals. Morphologically normal PB1 oocytes can be retrieved from all patients. However, most of the oocytes cannot be fertilized successfully. These findings confirmed our previous research and expanded the mutational spectrum of WEE2, making it a potential genetic diagnostic marker for those suffering from human fertilization failure.

A novel homozygous variant in NLRP5 is associate with human early embryonic arrest in a consanguineous Chinese family

“…Recently, mutations responsible for many of these novel Mendelian phenotypes have been identified. Mutations in TUBB8 (MIM: 616768) and PATL2 (MIM: 614661) were reported to cause oocyte maturation arrest, 10‐13 and mutations in WEE2 (MIM: 614084) was reported to result in fertilization failure 14,15 …”

Novel compound heterozygous mutation in WEE2 is associated with fertilization failure: case report of an infertile woman and literature review

“…Nearly all the patients with WEE2 mutations presented with complete obstacles in PN formation on day 1 (D1) from MII oocytes despite the use of ICSI or the calcium ionophore A23187 for activation. However, cases with mutation c.1228C > T, c.1576T > G and c.293_294ins presented with low fertilization rate and none normal cleavage embryos [ 11 , 12 , 14 ]. In our study, we identified a novel compound heterozygous mutation in WEE2 , expanding the mutation spectrum of this gene in fertilization failure.…”

Origins and mechanisms leading to aneuploidy in human eggs

“…7,82,83 Yet depending on their timing of occurrence, even these complex forms of mosaicism may not preclude development, and indeed may be preferentially excluded from the embryo during the process of blastocyst formation. 84,85 While explaining a small fraction (∼1%) of the total variance in aneu- oocyte meiosis inhibiting kinase (WEE2) [98][99][100][101][102] that may predispose women to a higher incidence of oocyte and embryonic aneuploidy at younger-than-average ages. The products of these genes are required for essential steps in oocyte development and meiosis.…”