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. 2025 Jun 20;15(2):100548.
doi: 10.5493/wjem.v15.i2.100548.

miRNA dysregulation in Duchenne muscular dystrophy comorbidities

Subhashree Sivakumar  1 , Archana Rajavel  1 , Venkataraman Viswanathan  2 , Evangeline Ann Daniel  3 , Prakash Gangadaran  4   5   6 , Raja Natesan Sella  7
Affiliations

miRNA dysregulation in Duchenne muscular dystrophy comorbidities

Subhashree Sivakumar et al. World J Exp Med. .

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

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Conflict of interest statement

Conflict-of-interest statement: The authors declared no potential conflict of interest concerning the research, authorship, and/or publication of this article.

Figures

Figure 1
Figure 1
Schematic representation of the disease-onset stages for the child exhibiting DMD, epilepsy, and ASD. ASD: Autism spectrum disorder; DMD: Duchenne muscular dystrophy.
Figure 2
Figure 2
Pedigree chart for three generations of the proband with Duchenne muscular dystrophy, autism spectrum disorder, and epilepsy.
Figure 3
Figure 3
The differential expression of miRNA represented as fold change across the 3 samples: Control, Duchenne muscular dystrophy (DMD+), and DMD++. A: miR-146a-3p; B: miR-146a-5p; C: miR-132-3p; D: miR-132-5p; E: miR-199a-5p. Significance is presented as aP ≤ 0.01 and bP ≤ 0.001. Data are presented as the mean ± SEM. DMD: Duchenne muscular dystrophy.
Figure 4
Figure 4
Variations in the lower limb of patients with dystrophy. A: Duchenne muscular dystrophy (DMD+); B: DMD++.
See this image and copyright information in PMC

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