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ORIGINAL RESEARCH article

Front. Med.
Sec. Obstetrics and Gynecology
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1462649

Whole exome sequencing identifies a novel mutation in Annexin A4 that is associated with recurrent spontaneous abortion

Provisionally accepted
Qian Ye Qian Ye 1Ying F. Liu Ying F. Liu 2*Jian X. Xia Jian X. Xia 1*Yong X. Chen Yong X. Chen 3*Li Zou Li Zou 4*Min H. Wu Min H. Wu 5*Dan D. Li Dan D. Li 5*Nian C. Xia Nian C. Xia 5*Ting Huang Ting Huang 5*Ying Cui Ying Cui 3*Yang Zou Yang Zou 2*
  • 1 Department of Traditional Chinese Medicine, Jiangxi Maternal and Child Health Hospital, Nanchang, China
  • 2 Central Laboratory, Jiangxi Maternal and Child Health Hospital, Nanchang, China
  • 3 Department of Traditional Chinese Medicine,, Jiangxi Maternal and Child Health Hospital, Nanchang, China
  • 4 Quality Control Office, Ganzhou People's Hospital, Ganzhou, Jiangxi Province, China
  • 5 Graduate School of Clinical Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi Province, China

The final, formatted version of the article will be published soon.

    Background: Recurrent spontaneous abortion (RSA) is a multifactorial disease, the exact causes of which are still unknown. Environmental, maternal, and genetic factors have been shown to contribute to this condition. The aim of this study was to investigate the presence of mutations in the ANXA4 gene in patients with RSA. Methods: Genomic DNA was extracted from 325 patients with RSA and 941 control women with a normal reproductive history for whole-exome sequencing (WES). The detected variants were annotated and filtered, and the pathogenicity of the variants was predicted through the SIFT online tool, functional enrichment analyses, Sanger sequencing validation, prediction of changes in protein structure, and evolutionary conservation analysis. Furthermore, plasmid construction, Western blotting, RT‒qPCR, and cell migration, invasion and adhesion assays were used to detect the effects of ANXA4 mutations on protein function. Results: An ANXA4 mutation (p.G8D) in 1 of the 325 samples from patients with RSA (RSA-219) was identified through WES. This mutation was not detected in 941 controls or included in public databases. Evolutionary conservation analysis revealed that the amino acid residue affected by the mutation (p.G8D) was highly conserved among 13 vertebrate species, and the SIFT program and structural modeling analysis predicted that this mutation was harmful. Furthermore, functional assays revealed that this mutation could inhibit cell migration, invasion and adhesion. Conclusion: Our study suggests that an unreported novel ANXA4 mutation (p.G8D) plays an important role in the pathogenesis of RSA and may contribute to the genetic diagnosis of RSA.

    Keywords: ANXA4 mutation, Recurrent spontaneous abortion, cell invasion, Migration, Adhesion

    Received: 10 Jul 2024; Accepted: 17 Sep 2024.

    Copyright: © 2024 Ye, Liu, Xia, Chen, Zou, Wu, Li, Xia, Huang, Cui and Zou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Ying F. Liu, Central Laboratory, Jiangxi Maternal and Child Health Hospital, Nanchang, China
    Jian X. Xia, Department of Traditional Chinese Medicine, Jiangxi Maternal and Child Health Hospital, Nanchang, China
    Yong X. Chen, Department of Traditional Chinese Medicine,, Jiangxi Maternal and Child Health Hospital, Nanchang, China
    Li Zou, Quality Control Office, Ganzhou People's Hospital, Ganzhou, Jiangxi Province, China
    Min H. Wu, Graduate School of Clinical Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China
    Dan D. Li, Graduate School of Clinical Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China
    Nian C. Xia, Graduate School of Clinical Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China
    Ting Huang, Graduate School of Clinical Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China
    Ying Cui, Department of Traditional Chinese Medicine,, Jiangxi Maternal and Child Health Hospital, Nanchang, China
    Yang Zou, Central Laboratory, Jiangxi Maternal and Child Health Hospital, Nanchang, China

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