"Novel variants in ZP1, ZP2 and ZP3 associated with empty follicle syndrome and abnormal zona pellucida"

作者全名："Sun, Liwei; Tong, Keya; Liu, Weiwei; Tian, Yin; Liu, Dongyun; Huang, Guoning; Li, Jingyu"

作者地址："[Sun, Liwei; Tong, Keya; Liu, Weiwei; Tian, Yin; Liu, Dongyun; Huang, Guoning; Li, Jingyu] Chongqing Med Univ, Ctr Reprod Med, Chongqing Key Lab Human Embryo Engn, Women & Childrens Hosp, Chongqing, Peoples R China; [Sun, Liwei; Tong, Keya; Liu, Weiwei; Tian, Yin; Liu, Dongyun; Huang, Guoning; Li, Jingyu] Chongqing Hlth Ctr Women & Children, Chongqing Clin Res Ctr Reprod Med, Chongqing, Peoples R China"

通信作者："Huang, GN; Li, JY (通讯作者)，Chongqing Med Univ, Ctr Reprod Med, Chongqing Key Lab Human Embryo Engn, Women & Childrens Hosp, Chongqing, Peoples R China.; Huang, GN; Li, JY (通讯作者)，Chongqing Hlth Ctr Women & Children, Chongqing Clin Res Ctr Reprod Med, Chongqing, Peoples R China."

来源：REPRODUCTIVE BIOMEDICINE ONLINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000992437800001

JCR分区：Q1

影响因子：3.7

年份：2023

卷号：46

期号：5

开始页：847

结束页：855

文献类型：Article

关键词：Abnormal zona pellucida; Empty follicle syndrome; Novel variants; ZP1; ZP2; ZP3

摘要："Research question: Which genetic variants might explain the causes of empty follicle syndrome (EFS) and abnormal zona pellucida (ZP) and affect the success of treatment with assisted reproductive technologies (ART)?Design: Whole-exome sequencing was performed in probands with EFS and abnormal ZP. Sanger sequencing was used for variant validation. Using HEK-293T cells, the effects of ZP1 and ZP2 variants on protein expression were explored by western blotting, and the effect of the ZP1 variant on protein location was investigated via immunofluorescence. The protein structure was also analysed to investigate the pathogenicity of variants.Results: A homozygous nonsense variant in ZP1 (c.874C>T, p.Gln292*) was detected in a patient with EFS. A novel homozygous frameshift variant in ZP2 (c.836_837delAG, p.Glu279Valfs*6) and a novel heterozygous missense variant in ZP3 (c.1159G>A, p.Val387Met) were identified in two patients with ZP morphological abnormalities, respectively. Western blotting and immunofluorescence analysis showed that the ZP1 variant results in a premature stop codon, leading to the truncated ZP1 protein. The ZP2 variant, which is situated in the N-terminus, triggers the degradation of a premature termination protein. Additionally, the patient with the ZP3 variant achieved clinical pregnancy following intracytoplasmic sperm injection treatment.Conclusions: These findings expand the mutational spectrum of ZP1, ZP2 and ZP3, and provide new evidence for genetic diagnosis of female infertility. The targeted genetic diagnosis of ZP genes is recommended to choose appropriate fertilization methods and improve success rates of treatment with ART."

基金机构：General Project of the Women and Children's Hospital of Chongqing Medical University [2021YJMS05]; General Project of the Chongqing Natural Science Foundation of China [cstc2021jcyj-msxmX0877]

基金资助正文：This study was supported by the General Project of the Women and Children's Hospital of Chongqing Medical University [2021YJMS05] and the General Project of the Chongqing Natural Science Foundation of China [cstc2021jcyj-msxmX0877].