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Insights and future directions of potential genetic therapy for Apert syndrome: A systematic review

Gene Therapy volume 28, pages 620–633 (2021)Cite this article

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Abstract

Apert syndrome is a genetic disorder characterised by craniosynostosis and structural discrepancy of the craniofacial region as well as the hands and feet. This condition is closely linked with fibroblast growth factor receptor-2 (FGFR2) gene mutations. Gene therapies are progressively being tested in advanced clinical trials, leading to a rise of its potential clinical indications. In recent years, research has made great progress in the gene therapy of craniosynostosis syndromes and several studies have investigated its influences in preventing/diminishing the complications of Apert syndrome. This article reviewed and exhibited different techniques of gene therapy and their influences in Apert syndrome progression. A systematic search was executed using electronic bibliographic databases including PubMed, EMBASE, ScienceDirect, SciFinder and Web of Science for all studies of gene therapy for Apert syndrome. The primary outcomes measurements vary from protein to gene expressions. According to the findings of included studies, we conclude that the gene therapy using FGF in Apert syndrome was critical in the regulation of suture fusion and patency, occurred via alterations in cellular proliferation. The superior outcome could be brought by biological therapies targeting the FGF/FGFR signalling. More studies in molecular genetics in Apert syndrome are recommended. This study reviews the current literature and provides insights to future possibilities of genetic therapy as intervention in Apert syndrome.

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Fig. 1: FGFR2 mutation and signaling pathways of Apert Syndrome.
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Acknowledgements

This work was supported by FRGS grant (FP103-2019A) from the Ministry of Higher Education, Malaysia (Ref: FRGS/1/2019/SKK10/UM/02/3).

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Author notes

  1. These authors contributed equally: Nisreen Mohammed Al-Namnam, Soher Nagi Jayash

Authors and Affiliations

  1. Department Oral Surgery, Faculty of Dentistry, University of Sana’a, Sana’a, Yemen

    Nisreen Mohammed Al-Namnam

  2. School of Dentistry, University of Birmingham, 5 Mill Pool Way, Edgbaston, Birmingham, UK

    Soher Nagi Jayash

  3. Department of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Firdaus Hariri & Zainal Ariff Abdul Rahman

  4. Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Mohammed Abdullah Alshawsh

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Al-Namnam, N.M., Jayash, S.N., Hariri, F. et al. Insights and future directions of potential genetic therapy for Apert syndrome: A systematic review. Gene Ther 28, 620–633 (2021). https://doi.org/10.1038/s41434-021-00238-w

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