卵子成熟障碍导致的女性原发性不孕症是临床面临的棘手问题。约40%的患者由TUBB8或PATL2基因突变所致，但绝大多数患者的致病原因仍不明确。MAD2L1BP是有丝分裂细胞周期的调控蛋白，但在人类减数分裂中的作用有待明确。我们前期在6例卵子MI期阻滞的患者中发现1例MAD2L1BP基因纯合性无义突变患者（发生率约16.7%）；该纯合性突变在ExAC及gnomAD数据库中未有记载。本项目拟对更多卵子成熟障碍病例进行该基因的突变筛查；研究该基因突变是否影响mRNA转录、蛋白表达及蛋白在卵子中的表达定位；该基因低表达或过表达、以及过表达突变型基因是否影响卵子成熟，以探索该基因突变导致卵子成熟障碍的致病机制。本项目旨在发现和鉴定新的常染色体隐性遗传卵子成熟障碍致病基因，为该病的基因诊断、遗传咨询及生育指导提供新的理论依据；也为卵子质量评估提供新的分子标记，为该类疾病的精准治疗提供新的分子靶点。

Female primary infertility caused by oocyte maturation arrest is a tough problem facing the clinical staffs. TUBB8 or PATL2 mutations present in about 40% of cases with oocyte maturation arrest, while the genetic causes are still unknown in the majority of cases with the disorder. Previously, we identified a homozygous nonsense mutation in MAD2L1BP gene in one of six (about 16.7%) patients with oocyte arrested at Metaphase I stage. This homozygous mutation is not record in the databases of ExAC and gnomAD. This study will carry out mutation analysis of MAD2L1BP in more cases of oocyte maturation arrest. Next, we will evaluate whether the gene mutation have an effect on mRNA transcription, protein expression and the distribution of the protein in oocytes, and evaluate the possible effects of down-regulation of the gene, overexpression of the gene and overexpression of the mutated gene on oocyte maturation in respective, to explore the pathogenic mechanism of the gene mutation causing oocyte maturation arrest. This project is expected to identify a novel causative gene for autosomal recessive oocyte maturation arrest, and this will provide a basis for the genetic diagnosis of the disorder, genetic counseling and reproductive counseling; and it also will provide a new molecular biomarker for evaluation of oocyte quality, and a new molecular target for the precision treatment of this disease.