Basic Study
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World J Exp Med. Jun 20, 2025; 15(2): 100548
Published online Jun 20, 2025. doi: 10.5493/wjem.v15.i2.100548
miRNA dysregulation in Duchenne muscular dystrophy comorbidities
Subhashree Sivakumar, Archana Rajavel, Venkataraman Viswanathan, Evangeline Ann Daniel, Prakash Gangadaran, Raja Natesan Sella
Subhashree Sivakumar, Archana Rajavel, Raja Natesan Sella, Department of Genetic Engineering, SRM Institute of Science and Technology, Chennai 603203, Tamil Nādu, India
Venkataraman Viswanathan, Department of Pediatric Neurology, Apollo Children's Hospital, Chennai 600006, Tamil Nādu, India
Evangeline Ann Daniel, Department of HIV/AIDS, National Institute for Research in Tuberculosis, Chennai 600031, Tamil Nādu, India
Prakash Gangadaran, BK21 Four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
Prakash Gangadaran, Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
Prakash Gangadaran, Cardiovascular Research Institute, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
Co-corresponding authors: Prakash Gangadaran and Raja Natesan Sella.
Author contributions: Sivakumar S performed all the experiments and wrote the manuscript; Sivakumar S and Natesan Sella R conducted the data analysis; Rajavel A and Natesan Sella R conceptualized the study; Venkataraman V performed clinical diagnosis; Daniel EA assisted in performing the qRT-PCR; Gangadaran P and Natesan Sella R reviewed and edited the manuscript; all authors have read and agreed to publish this manuscript.
Institutional review board statement: The study was reviewed and approved by the ethics committee of Apollo Children’s Hospital (No. ACH-OTH-001/11-20).
Conflict-of-interest statement: The authors declared no potential conflict of interest concerning the research, authorship, and/or publication of this article.
Data sharing statement: The data of the participants in the study were anonymized and shared in the article. No additional data are available.
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: Raja Natesan Sella, PhD, Associate Professor, Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, Chennai 603203, Tamil Nādu, India. rajan3@srmist.edu.in
Received: August 21, 2024
Revised: December 19, 2024
Accepted: January 2, 2025
Published online: June 20, 2025
Processing time: 238 Days and 22.1 Hours
Abstract
BACKGROUND

Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by mutations in the dystrophin gene. DMD is reported to coexist with other comorbidities, although the occurrence of the triad, autism spectrum disorder (ASD), and epilepsy is very rare. Indeed, only one case of the triad has currently been reported. Here, we present a detailed case report of a ten-year-old boy with DMD, ASD, and epilepsy. We also investigated the dysregulation of miRNAs in this unusual triad (represented as DMD++) compared with a healthy individual and a DMD patient (represented as DMD+) without autism.

AIM

To understand the differential expression of miRNAs in rare comorbid DMD cases.

METHODS

The Sequin Form Board test, Gesell's drawing test, multiplex ligation probe amplification, and Vineland Social Maturity Scale were applied to confirm the DMD and ASD. Total RNA was isolated from samples using TRIzol. cDNA was synthesized using the Mir-X™ miRNA First-Strand Synthesis kit. qRT-PCR was performed using SYBR Advantage qPCR Premix. The results were statistically analyzed using one-way analysis of variance with Tukey's t-test.

RESULTS

miR-146a-5p and miR-132-5p showed significant downregulation in both patient samples. miR-199a-5p and miR-146a-3p showed no change in expression between the diseased and controls. miR-132-3p showed downregulation only in the DMD+ sample (0.21 ± 0.04). The decrease in miR-132-3p can result in failed silencing of the phosphatase and tensin homolog-mediated apoptotic pathway, leading to severe skeletal muscle atrophy. Here, the downregulation of miR-132-3p in DMD+ is consistent with severe muscle loss and higher disease progression than that in DMD++. DMD++ has slower disease progression, and the expression of miRNA involved in inflammatory and apoptotic responses is more similar to that of the control.

CONCLUSION

Our study shows marked difference in miRNA expression in this rare case of DMD with autism and epilepsy. These miRNAs also serve as regulators of several muscle regeneration, apoptosis, and inflammatory pathways. This study shows the significance of studying miRNAs in such rare cases in a larger cohort to progress in several intervention treatments utilizing miRNAs.

Keywords: Duchenne muscular dystrophy; Dystrophin; miRNA; Autism spectrum disorder; Phosphatase and tensin; Inflammatory response

Core Tip: This study presents a rare case of a ten-year-old boy with Duchenne muscular dystrophy (DMD) coexisting with autism spectrum disorder and epilepsy. By investigating the differential expression of miRNAs, we identified a significant downregulation of miR-132-3p in the DMD patient compared to the comorbid DMD case. This suggests that miR-132-3p downregulation may have contributed to accelerated muscle atrophy through failed silencing of the phosphatase and tensin homolog-mediated apoptotic pathway. Our findings emphasize the importance of studying such rare DMD comorbidities to enhance understanding of disease heterogeneity and improve diagnosis and treatment strategies.