[Analysis of a Chinese pedigree with female infertility due to WEE2 gene c.495del homozygous frameshifting variant induced fertilization disorder].

Abstract

Objective: To explore the genetic basis for a patient with repeated fertilization failure during assisted reproductive therapy, and to identify the source and mode of mutation.

Methods: A couple treated at the Center for Reproductive Medicine, Gansu Provincial Maternal and Child Health Care Hospital in January 2024 for infertility with incomplete left tube obstruction was selected as the study subject. Relevant clinical data was collected. The couple was subjected to whole exome sequencing (WES), and the candidate variant was verified by Sanger sequencing of their family members and bioinformatic analysis.

Results: WES has identified a homozygous c.495del frameshifting mutation of the WEE2 gene in the female partner, whilst no relevant variant was suspected in the male partner. The elder brother of the female partner was homozygous for the above variant, while her parents, maternal and paternal aunts, uncle, grandmother, and grandmother were heterozygous for it. Based on the guidelines from the American College of Medical Genetics and Genomics, above variant was rated to be pathogenic.

Conclusion: The homozygous c.495del frameshifting mutation of the WEE2 gene probably underlay the oocyte fertilization disorder in this couple, which has conformed to an autosomal recessive inheritance.