DLGAP5 mutations Disrupt Normal Chromosome Segregation and Spindle Formation of human Oocyte Meiosis and Lead to Female Infertility

作者：Meng Wang, Zhou Li, Juepu Zhou, Rui Long, Qingsong Xi, Hong Gao, Youzhu Li, Lei Jin, Lixia Zhu · 发表于：MedComm · 年份：2025 · DOI：10.1002/mco2.70224 · 被引用次数：3 · 研究领域：Reproductive Biology and Fertility、Renal and related cancers、Prenatal Screening and Diagnostics

Dear Editor, Nowadays, approximately one out of six couples of reproductive age are confronted with infertility. Assisted reproductive technology (ART) constitutes one of the most effective measures to address this issue; however, in certain instances, ART fails [1]. Moreover, some patients experience recurrent ART failure with a uniform phenotype, suggesting a genetic component to their condition [2]. Recently, the advent of whole-exome sequencing (WES) has led to the identification of an increasing number of genetic causes of human infertility [3]. However, the genetic underpinnings of a significant proportion of cases remain enigmatic [3]. Consequently, it is imperative to elucidate the potential genetic determinants of ART failure and to identify novel genetic etiologies for genetic counseling, as well as for the diagnosis and treatment of infertility patients. In this study, we observed a pair of sisters who were undergoing ART. Both of the sisters were diagnosed with unexplained primary infertility. Following numerous in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) cycles, they failed to conceive, and the majority of their oocytes were immature. Subsequent genetic analysis identified a homozygous nonsense mutation c.1101C>G (p.Tyr367*) in DLGAP5 in both sisters. The parents of the sisters are known to be from a consanguineous marriage family (family 1). The father was a heterozygous carrier, and the mother had already passed away (Figure 1A)....