Espectro mutacional de la distrofia muscular de Duchenne en España: estudio de 284 casos

Viéitez, Irene; Gallano, P.; González-Quereda, L.; Borrego, Salud; Marcos, Irene; Millán, JM; Jairo, T.; Prior, C.; Molano, Jesús; Trujillo-Tiebas, M J; Gallego-Merlo, J.; García-Barcina, María; Fenollar, M.; Navarro, Carmen

doi:10.1016/j.nrl.2015.12.009

Cited by 23 publications

(7 citation statements)

References 41 publications

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“…During Muslim immigration from the Levant, Africa, in Ancient Islamic times, much intermarriage reinforced gene flow of the DMD gene to the Saudi people. This has likely influenced the prevalence of different Mendelian patterns, particularly X-linked types, exemplified by the consistency of data for DMD rearrangements between our study and a recent Spanish cohort study (46.1%, 131/284 for deletions and 56/284, 19.7% for duplications) [ 52 ].…”

Section: Discussionsupporting

confidence: 68%

Molecular characterization of exonic rearrangements and frame shifts in the dystrophin gene in Duchenne muscular dystrophy patients in a Saudi community

Elhawary

Jiffri

Jambi³

et al. 2018

Hum Genomics

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BackgroundIn individuals with Duchenne muscular dystrophy (DMD), exon skipping treatment to restore a wild-type phenotype or correct the frame shift of the mRNA transcript of the dystrophin (DMD) gene are mutation-specific. To explore the molecular characterization of DMD rearrangements and predict the reading frame, we simultaneously screened all 79 DMD gene exons of 45 unrelated male DMD patients using a multiplex ligation-dependent probe amplification (MLPA) assay for deletion/duplication patterns. Multiplex PCR was used to confirm single deletions detected by the MLPA.ResultsThere was an obvious diagnostic delay, with an extremely statistically significant difference between the age at initial symptoms and the age of clinical evaluation of DMD cases (t value, 10.3; 95% confidence interval 5.95–8.80, P < 0.0001); the mean difference between the two groups was 7.4 years. Overall, we identified 147 intragenic rearrangements: 46.3% deletions and 53.7% duplications. Most of the deletions (92.5%) were between exons 44 and 56, with exon 50 being the most frequently involved (19.1%). Eight new rearrangements, including a mixed deletion/duplication and double duplications, were linked to seven cases with DMD. Of all the cases, 17.8% had duplications with no hot spots. In addition, confirmation of the reading frame hypothesis helped account for new DMD rearrangements in this study. We found that 81% of our Saudi patients would potentially benefit from exon skipping, of which 42.9% had a mutation amenable to skipping of exon 51.ConclusionsOur study could generate considerable data on mutational rearrangements that may promote future experimental therapies in Saudi Arabia.Electronic supplementary materialThe online version of this article (10.1186/s40246-018-0152-8) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 68%

Molecular characterization of exonic rearrangements and frame shifts in the dystrophin gene in Duchenne muscular dystrophy patients in a Saudi community

Elhawary

Jiffri

Jambi³

et al. 2018

Hum Genomics

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“…Genetic analysis of DMD patients showed that large deletions are the most common type of mutations worldwide (64% in Oceania, 66% in Europe, 70% in Americas, 72% in Asia, and 88% in Africa). Population-based cohort studies (Chinese [ 16 ], Spanish [ 17 ], and Italian [ 18 ]) also manifested racial characteristics of DMD mutation types.…”

Section: Genetic Pathogenesis Of Dmdmentioning

confidence: 99%

Therapeutic Strategies for Duchenne Muscular Dystrophy: An Update

Sun

Shen

Zhang

et al. 2020

Genes

114

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Neuromuscular disorders encompass a heterogeneous group of conditions that impair the function of muscles, motor neurons, peripheral nerves, and neuromuscular junctions. Being the most common and most severe type of muscular dystrophy, Duchenne muscular dystrophy (DMD), is caused by mutations in the X-linked dystrophin gene. Loss of dystrophin protein leads to recurrent myofiber damage, chronic inflammation, progressive fibrosis, and dysfunction of muscle stem cells. Over the last few years, there has been considerable development of diagnosis and therapeutics for DMD, but current treatments do not cure the disease. Here, we review the current status of DMD pathogenesis and therapy, focusing on mutational spectrum, diagnosis tools, clinical trials, and therapeutic approaches including dystrophin restoration, gene therapy, and myogenic cell transplantation. Furthermore, we present the clinical potential of advanced strategies combining gene editing, cell-based therapy with tissue engineering for the treatment of muscular dystrophy.

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“…In Mexican-Mestizo patients, mutations in exon 51 are more prevalent 9 ; however, 78% of deletion mutations in Indonesian patients occur in exons 43 to 52 10 . Exons 51 and 45 are reported as hotspots mutation exons in Spain 11 . Among Iranian patients, DMD gene mutations diversify.…”

Section: Discussionmentioning

confidence: 98%

Using CRISPR/Cas9 System to Knock out Exon 48 in DMD Gene

Dara¹,

Razban²,

Talebzadeh³

et al. 2021

AJMB

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Background: Out of frame mutations in DMD gene cause Duchenne Muscular Dystrophy (DMD) which is a neuromuscular progressive genetic disorder. In DMD patients, lack of dystrophin causes progressive muscle degeneration, which results in heart and respiratory failure leading to premature death. At present, there is no certain treatment for DMD. DMD gene is the largest gene in human genome by 2.2 mega base pairs and contains 79 exons. In the past few years, gene therapy has been considered a promising DMD treatment, and among various gene-editing technologies, CRISPR/Cas9 system is shown to be more precise and reliable. The aim of this study was to assess the possibility of knocking out exon 48 by using a pair of sgRNAs. Methods: A pair of guide RNAs (gRNAs) was designed to cleave DMD gene and induce deletion of exon 48. gRNAs were transfected to the HEK-293 cell line and then the deletion in genomic DNA was analyzed by PCR and subsequent Sanger sequencing. Results: Exon 48 was successfully deleted and therefore exon 47 was joined to exon 49. Conclusion: This result indicated that CRISPR/Cas9 system could be used to edit DMD gene precisely.

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Espectro mutacional de la distrofia muscular de Duchenne en España: estudio de 284 casos

Cited by 23 publications

References 41 publications

Molecular characterization of exonic rearrangements and frame shifts in the dystrophin gene in Duchenne muscular dystrophy patients in a Saudi community

Molecular characterization of exonic rearrangements and frame shifts in the dystrophin gene in Duchenne muscular dystrophy patients in a Saudi community

Therapeutic Strategies for Duchenne Muscular Dystrophy: An Update

Using CRISPR/Cas9 System to Knock out Exon 48 in DMD Gene

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