Dmd, encoding the protein dystrophin, is a crucial gene. Dystrophin is a structural protein located on the cytoplasmic face of the plasma membrane of muscle fibers, which is part of the dystrophin glycoprotein complex (DGC). It mechanically reinforces the sarcolemma and stabilizes the DGC, preventing contraction-mediated muscle degradation, thus maintaining the integrity of muscle fibres and protecting them from damage [2,5,6]. Mutations in Dmd cause Duchenne and Becker muscular dystrophies (DMD/BMD), making it of great biological importance in understanding muscle-related diseases [1,2,3,4,7].

Exonic deletions and duplications within Dmd are the main pathogenic variants in DMD/BMD. Deletions most frequently occur in the genomic region encompassing exons 45-55 [1]. Different Dmd mutations result in various phenotypes and disease severity, with Duchenne muscular dystrophy being a severe form characterized by progressive muscle degeneration, respiratory and cardiac complications [2,3]. Some Dmd deletions can lead to milder or even asymptomatic phenotypes, and specific genetic profiles may be associated with these mild phenotypes [4]. Also, in DMD/BMD patients with cardiac dysfunction, a higher frequency of involvement of exons 45 and 46 was found, which might predict cardiac involvement [7].

In conclusion, Dmd is essential for maintaining muscle fibre integrity. Studies on its mutations through various models help understand the genotype-phenotype correlations in DMD/BMD, especially in relation to muscle and cardiac phenotypes. This knowledge is crucial for developing targeted therapies for these muscle-wasting diseases [3,4,7].

References:

1. Ling, Chao, Dai, Yi, Fang, Li, Wang, Kai, Zhang, Xue. 2019. Exonic rearrangements in DMD in Chinese Han individuals affected with Duchenne and Becker muscular dystrophies. In Human mutation, 41, 668-677. doi:10.1002/humu.23953. https://pubmed.ncbi.nlm.nih.gov/31705731/

2. Salmaninejad, Arash, Jafari Abarghan, Yousef, Bozorg Qomi, Saeed, Talebi, Samaneh, Mojarrad, Majid. 2020. Common therapeutic advances for Duchenne muscular dystrophy (DMD). In The International journal of neuroscience, 131, 370-389. doi:10.1080/00207454.2020.1740218. https://pubmed.ncbi.nlm.nih.gov/32241218/

3. Gatto, Francesca, Benemei, Silvia, Piluso, Giulio, Bello, Luca. 2024. The complex landscape of DMD mutations: moving towards personalized medicine. In Frontiers in genetics, 15, 1360224. doi:10.3389/fgene.2024.1360224. https://pubmed.ncbi.nlm.nih.gov/38596212/

4. Fortunato, Fernanda, Tonelli, Laura, Farnè, Marianna, Selvatici, Rita, Ferlini, Alessandra. 2024. DMD deletions underlining mild dystrophinopathies: literature review highlights phenotype-related mutation clusters and provides insights about genetic mechanisms and prognosis. In Frontiers in neurology, 14, 1288721. doi:10.3389/fneur.2023.1288721. https://pubmed.ncbi.nlm.nih.gov/38288333/

5. Elangkovan, Nertiyan, Dickson, George. . Gene Therapy for Duchenne Muscular Dystrophy. In Journal of neuromuscular diseases, 8, S303-S316. doi:10.3233/JND-210678. https://pubmed.ncbi.nlm.nih.gov/34511510/

6. Thapa, Sangharsha, Elhadidy, Shaymaa, Asakura, Atsushi. 2023. Vascular therapy for Duchenne muscular dystrophy (DMD). In Faculty reviews, 12, 3. doi:10.12703/r/12-3. https://pubmed.ncbi.nlm.nih.gov/36873982/

7. Zhou, Huan, Fu, Manli, Mao, Bing, Yuan, Li. 2020. Cardiac Phenotype-Genotype Associations in DMD/BMD: A Meta-Analysis and Systematic Review. In Pediatric cardiology, 42, 189-198. doi:10.1007/s00246-020-02470-4. https://pubmed.ncbi.nlm.nih.gov/33037470/