Novel mutations in ZP1 and ZP2 cause primary infertility due to empty follicle syndrome and abnormal zona pellucida

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 s...

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Bibliographic Details
Published in:Journal of assisted reproduction and genetics 2020-11, Vol.37 (11), p.2853-2860
Main Authors: Luo, Geng, Zhu, Lixia, Liu, Zhenxing, Yang, Xue, Xi, Qingsong, Li, Zhou, Duan, Jinliang, Jin, Lei, Zhang, Xianqin
Format: Article
Language:English
Subjects:
Genes
Genetic analysis
Genetic screening
Genetics
Gynecology
Human Genetics
Infertility
Medicine
Medicine & Public Health
Mutants
Mutation
Oocytes
Reproductive Medicine
Zona pellucida
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Summary: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.
ISSN:1058-0468
1573-7330
DOI:10.1007/s10815-020-01926-z