Systematic Reviews
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Pediatr. Sep 9, 2024; 13(3): 98468
Published online Sep 9, 2024. doi: 10.5409/wjcp.v13.i3.98468
Decoding the genetic landscape of autism: A comprehensive review
Mohammed Al-Beltagi, Nermin Kamal Saeed, Adel Salah Bediwy, Eman A Bediwy, Reem Elbeltagi
Mohammed Al-Beltagi, Department of Pediatric, Faculty of Medicine, Tanta University, Alghrabia, Tanta ‎31511‎, Egypt
Mohammed Al-Beltagi, Department of Pediatric, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
Nermin Kamal Saeed, Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, ‎Ministry of Health, Kingdom of Bahrain, Manama 12, Bahrain
Nermin Kamal Saeed, Medical Microbiology Section, Department of Pathology, Irish Royal College of Surgeon, Muharraq, Busaiteen 15503, Bahrain
Adel Salah Bediwy, Department of Pulmonology, Faculty of Medicine, Tanta University, Alghrabia, Tanta ‎‎ 31527, Egypt
Adel Salah Bediwy, Department of Pulmonology, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
Eman A Bediwy, Internal Medicine, Faculty of Medicine, Tanta University, Algharbia, Tanta 31527, Egypt
Reem Elbeltagi, Department of Medicine, The Royal College of Surgeons in Ireland-Bahrain, ‎Muharraq, Busiateen 15503, Bahrain
Co-first authors: Mohammed Al-Beltagi and Nermin Kamal Saeed.
Author contributions: Al-Biltagi M coordinated the project, contributed to the design, supervised the literature search, and ensured data integrity; Saeed NK was involved in the methodology, literature screening, data extraction, and manuscript writing; Bediwy AS participated in the literature search, data extraction, preliminary analyses, and manuscript drafting; Bediwy EA oversaw technical aspects, quality control, and statistical analysis and contributed to the manuscript, particularly in the analysis sections; Elbeltagi R addressed ethical considerations, contributed to the literature search and data extraction, and provided insights during data synthesis. All authors critically revised the manuscript and approved the final version, agreeing to be accountable for all aspects of the work. Al-Biltagi M and Saeed NK contributed equally to this work as co-first authors.
Conflict-of-interest statement: The authors declare that there are no conflicts of interest regarding the publication of this manuscript.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mohammed Al-Beltagi, MBChB, MD, PhD, Academic Editor, Chairman, Full Professor, Research Scientist, Department of Pediatric, Faculty of Medicine, Tanta University, Al-Bahr Street, The Medical Complex, Alghrabia, Tanta ‎31511‎, Egypt. mbelrem@hotmail.com
Received: June 26, 2024
Revised: July 29, 2024
Accepted: August 1, 2024
Published online: September 9, 2024
Processing time: 64 Days and 9.6 Hours
Abstract
BACKGROUND

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by heterogeneous symptoms and genetic underpinnings. Recent advancements in genetic and epigenetic research have provided insights into the intricate mechanisms contributing to ASD, influencing both diagnosis and therapeutic strategies.

AIM

To explore the genetic architecture of ASD, elucidate mechanistic insights into genetic mutations, and examine gene-environment interactions.

METHODS

A comprehensive systematic review was conducted, integrating findings from studies on genetic variations, epigenetic mechanisms (such as DNA methylation and histone modifications), and emerging technologies [including Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 and single-cell RNA sequencing]. Relevant articles were identified through systematic searches of databases such as PubMed and Google Scholar.

RESULTS

Genetic studies have identified numerous risk genes and mutations associated with ASD, yet many cases remain unexplained by known factors, suggesting undiscovered genetic components. Mechanistic insights into how these genetic mutations impact neural development and brain connectivity are still evolving. Epigenetic modifications, particularly DNA methylation and non-coding RNAs, also play significant roles in ASD pathogenesis. Emerging technologies like CRISPR-Cas9 and advanced bioinformatics are advancing our understanding by enabling precise genetic editing and analysis of complex genomic data.

CONCLUSION

Continued research into the genetic and epigenetic underpinnings of ASD is crucial for developing personalized and effective treatments. Collaborative efforts integrating multidisciplinary expertise and international collaborations are essential to address the complexity of ASD and translate genetic discoveries into clinical practice. Addressing unresolved questions and ethical considerations surrounding genetic research will pave the way for improved diagnostic tools and targeted therapies, ultimately enhancing outcomes for individuals affected by ASD.

Keywords: Autism spectrum disorder; Genetics; Epigenetics; Clustered Regularly Interspaced Short Palindromic Repeats-Cas9; Gene-environment interactions; Personalized medicine

Core Tip: This review synthesizes current knowledge on the genetic and epigenetic factors contributing to autism spectrum disorder (ASD). It highlights the complexity of ASD's genetic architecture and the role of epigenetic mechanisms such as DNA methylation and non-coding RNAs in disease pathogenesis. Emerging technologies like Clustered Regularly Interspaced Short Palindromic Repeats-Cas9 and advanced bioinformatics are pivotal for advancing our understanding of ASD. Collaborative research efforts are crucial for integrating diverse disciplines and international data, aiming to translate genetic insights into personalized therapies. Addressing unresolved questions and ethical considerations will be essential for maximizing the clinical utility of genetic discoveries in improving outcomes for individuals with ASD.