Purpose

Mutations in the zona pellucida glycoprotein genes have been reported to be associated with empty follicle syndrome (EFS) and abnormal zona pellucida (ZP). In this study, we performed genetic analysis in the patients with female infertility due to abnormal zona pellucida and empty follicle syndrome to identify the disease-causing gene mutations in these patients.

Methods

We characterized three patients from two independent families who had suffered from empty follicle syndrome or abnormal zona pellucida. Whole exome sequencing and Sanger sequencing were used to identify the mutations in the families. Western blot was used to check the expression of wild type and mutant disease genes.

Results

We identified two novel mutations in these patients, including a novel compound heterozygous mutation (c.507delC, p. His170fs; c.239 G>A, p. Cys80Tyr and c.241 T>C, p. Tyr81His) in ZP1 gene and a compound mutation in ZP2 gene (c.860_861delTG, p.Val287fs and c.1924 C>T, p.Arg642Ter). Expression of the mutant ZP1 protein (p. Cys80Tyr and p. Tyr81His) is significantly decreased compared with the wild-type ZP1. Other three mutations produce truncated proteins.

Conclusions

Our findings expand the mutational spectrum of ZP1 and ZP2 genes associated with EFS and abnormal oocytes and provide new support for the genetic diagnosis of female infertility.

中文翻译：

---

由于空卵泡综合征和异常透明带，ZP1 和 ZP2 中的新突变导致原发性不孕症。

目的

据报道，透明带糖蛋白基因的突变与空卵泡综合征 (EFS) 和异常透明带 (ZP) 相关。在本研究中，我们对透明带异常和空卵泡综合征导致的女性不孕症患者进行了基因分析，以确定这些患者的致病基因突变。

方法

我们对来自两个独立家庭的三名患有空卵泡综合征或异常透明带的患者进行了表征。全外显子组测序和Sanger测序用于鉴定家族中的突变。Western印迹用于检查野生型和突变疾病基因的表达。

结果

我们在这些患者中发现了两个新的突变，包括ZP1基因中的一个新的复合杂合突变（c.507delC，p. His170fs；c.239 G>A，p. Cys80Tyr 和 c.241 T>C，p. Tyr81His）和ZP2基因中的复合突变（c.860_861delTG、p.Val287fs 和 c.1924 C>T、p.Arg642Ter）。与野生型 ZP1 相比，突变型 ZP1 蛋白（p. Cys80Tyr 和 p. Tyr81His）的表达显着降低。其他三个突变产生截短的蛋白质。

结论

我们的研究结果扩展了与 EFS 和异常卵母细胞相关的ZP1和ZP2基因的突变谱，并为女性不育的基因诊断提供了新的支持。