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

• Published in: BMC women's health Vol. 20; no. 1; p. 246
• Main Authors: Tian, Ye, Wang, Guojie, Wang, Jin, Mu, Xiaohuan, Chen, Haixia, Song, Xueru, Bai, Xiaohong
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 04.11.2020; BioMed Central; BMC
• Subjects: Adult; Artificial oocyte activation; Case Report; Case reports; Case studies; Cell Cycle Proteins - genetics; Female; Female infertility; Gene mutation; Genetic aspects; Human fertilization failure; Human fertilization in vitro; Humans; Infertility; Infertility, Female - genetics; Infertility, Female - therapy; Kinases; Mutation; Novel variants; Obstetrical research; Patient outcomes; Protein-Tyrosine Kinases - genetics; Sperm Injections, Intracytoplasmic; Treatment Failure; WEE2; Women; Womens health; China; United States > US; Human fertilization failure; Artificial oocyte activation; WEE2; Novel variants
• ISSN: 1472-6874; 1472-6874
• DOI: 10.1186/s12905-020-01111-5

Fertilization failure after intracytoplasmic sperm injection continues to affect couples and the etiology is not well-understood. We characterized a couple with 2-year history of primary unexplained infertility. Three different assisted reproduction attempts (IVF + rescue ICSI, ICSI and ICSI-AOA) showed repeated fertilization failure for MII oocyte retrieval after controlled ovarian hyperstimulation. After whole-exome sequencing and sanger sequencing of the couple and their family members, variant pathogenicity was assessed using SIFT, PolyPhen2, Mutation Taster, and Human Splicing Finder software. We identified novel compound heterozygous mutations, c.1535 + 3A > G and c.946C > T (p. Leu316Phe), in WEE2 in the female proband. Trios analysis of the variations revealed an autosomal recessive pattern. c.1535 + 3A > G in WEE2 was predicted to break the wild-type donor site and affect splicing, and the missense mutation c.946C > T (p. Leu316Phe) of WEE2 was predicted to be pathogenic. A novel compound heterozygous mutation in WEE2 was identified in an infertile female who experienced repeated fertilization failure even after ICSI-AOA. These novel mutations in WEE2 provided genetic evidence for fertilization failure.