Identification of Novel Mutations in CDC20: Expanding the Mutational Spectrum for Female Infertility.

Lin Zhao,Weijie Wang,Lei Wang,Qiaoli Li,Jie Dong,Jiawei Zhu,Yiming Sun,Yao Chen,Yanping Kuang,Zhou Zhou,Zhihua Zhang,Jian Mu,Ruyi Liu,Yichun Guan,Yang Zeng,Ling Wu,Biaobang Chen,Jing Du,Tianyu Wu,Qing Sang,Jianxing Hu ,Qingyu Meng

doi:10.3389/fcell.2021.647130

Abstract

Oocyte maturation and fertilization are fundamental processes for successful human reproduction, and abnormalities in these processes will cause infertility. Recently, we identified biallelic mutations in CDC20 that are responsible for human oocyte maturation arrest, fertilization failure, and early embryonic development arrest. In this study, we screened for further CDC20 mutations in a new cohort of patients with abnormalities in oocyte maturation, fertilization, and early embryonic development. Through whole-exome sequencing, we identified the four novel mutations c.887G > A (p. Arg296Gln), c.964C > T (p.Arg322∗), c.1155G > C (p.Trp385Cys), and c.330 + 1G > A (p. Glu111Ilefs∗36) and one previously reported mutation c.965G > A (p.Arg322Gln) in CDC20 in four infertile individuals from three independent families. The patients had different phenotypes of oocyte maturation arrest and fertilization failure resulting from the different mutations. This study confirms our previous research and expands the spectrum of known mutations in CDC20, providing new evidence supporting the function of CDC20 in the genetic etiology of female infertility characterized by oocyte maturation arrest and fertilization failure.

Highlights

Successful human reproduction requires normal oocytes maturation, fertilization, and embryonic development, and any defects in the processes of oocyte maturation and fertilization will cause female infertility
Assisted reproduction technology (ART) is an effective treatment for infertility in which mature oocytes are fertilized with sperms through co-incubation called in vitro fertilization (IVF), or through direct injection of a single sperm under microscopic visualization, Novel Mutations in CDC20 called intracytoplasmic sperm injection (ICSI; Palermo et al, 1992; Myers et al, 2008)
We identified several mutations that impaired the normal function of CDC20, which resulted in female infertility due to abnormal oocyte maturation, fertilization, or early embryonic development (Zhao et al, 2020b)

Summary

Introduction

Successful human reproduction requires normal oocytes maturation, fertilization, and embryonic development, and any defects in the processes of oocyte maturation and fertilization will cause female infertility. Assisted reproduction technology (ART) is an effective treatment for infertility in which mature oocytes are fertilized with sperms through co-incubation called in vitro fertilization (IVF), or through direct injection of a single sperm under microscopic visualization, Novel Mutations in CDC20 called intracytoplasmic sperm injection (ICSI; Palermo et al, 1992; Myers et al, 2008). We demonstrated that biallelic mutations in CDC20 (HGNC:1723) are responsible for abnormalities in human oocyte maturation, fertilization, and early embryonic development (Zhao et al, 2020b). Despite these findings, the genetic basis for a large number of infertile patients remains to be elucidated

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Results

Conclusion