دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Novel variants in ZP1, ZP2 and ZP3 associated with empty follicle syndrome and abnormal zona pellucida.
المؤلفون: Sun L; Chongqing Key Laboratory of Human Embryo Engineering, Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University, Chongqing, China; Chongqing Clinical Research Center for Reproductive Medicine, Chongqing Health Center for Women and Children, Chongqing, China., Tong K; Chongqing Key Laboratory of Human Embryo Engineering, Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University, Chongqing, China; Chongqing Clinical Research Center for Reproductive Medicine, Chongqing Health Center for Women and Children, Chongqing, China., Liu W; Chongqing Key Laboratory of Human Embryo Engineering, Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University, Chongqing, China; Chongqing Clinical Research Center for Reproductive Medicine, Chongqing Health Center for Women and Children, Chongqing, China., Tian Y; Chongqing Key Laboratory of Human Embryo Engineering, Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University, Chongqing, China; Chongqing Clinical Research Center for Reproductive Medicine, Chongqing Health Center for Women and Children, Chongqing, China., Liu D; Chongqing Key Laboratory of Human Embryo Engineering, Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University, Chongqing, China; Chongqing Clinical Research Center for Reproductive Medicine, Chongqing Health Center for Women and Children, Chongqing, China., Huang G; Chongqing Key Laboratory of Human Embryo Engineering, Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University, Chongqing, China; Chongqing Clinical Research Center for Reproductive Medicine, Chongqing Health Center for Women and Children, Chongqing, China. Electronic address: gnhuang217@sina.com., Li J; Chongqing Key Laboratory of Human Embryo Engineering, Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University, Chongqing, China; Chongqing Clinical Research Center for Reproductive Medicine, Chongqing Health Center for Women and Children, Chongqing, China. Electronic address: cqtnljy@gmail.com.
المصدر: Reproductive biomedicine online [Reprod Biomed Online] 2023 May; Vol. 46 (5), pp. 847-855. Date of Electronic Publication: 2023 Jan 16.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101122473 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1472-6491 (Electronic) Linking ISSN: 14726483 NLM ISO Abbreviation: Reprod Biomed Online Subsets: MEDLINE
أسماء مطبوعة: Publication: <2009->: Amsterdam : Elsevier
Original Publication: Cambridge, UK : Reproductive Healthcare Ltd.
مواضيع طبية MeSH: Zona Pellucida*/chemistry , Zona Pellucida*/metabolism , Ovarian Diseases*/genetics , Ovarian Diseases*/metabolism, Pregnancy ; Humans ; Male ; Female ; Zona Pellucida Glycoproteins/genetics ; Zona Pellucida Glycoproteins/metabolism ; Semen ; Heterozygote ; Mutation
مستخلص: 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.
(Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
فهرسة مساهمة: Keywords: Abnormal zona pellucida; Empty follicle syndrome; Novel variants; ZP1; ZP2; ZP3
المشرفين على المادة: 0 (Zona Pellucida Glycoproteins)
0 (ZP1 protein, human)
0 (ZP2 protein, human)
0 (ZP3 protein, human)
تواريخ الأحداث: Date Created: 20230317 Date Completed: 20230504 Latest Revision: 20230511
رمز التحديث: 20240628
DOI: 10.1016/j.rbmo.2023.01.010
PMID: 36931917
قاعدة البيانات: MEDLINE
الوصف
تدمد:1472-6491
DOI:10.1016/j.rbmo.2023.01.010