Expanding the Molecular Genetic Landscape of Dystrophinopathies and Associated Phenotypes

<b>Background/Objectives</b>: X-linked dystrophinopathies are a group of neuromuscular diseases caused by pathogenic variants in the <i>DMD</i> gene (MIM *300377). Duchenne muscular dystrophy (DMD; MIM #310200) is the most common inherited muscular dystrophy. <b>Methods...

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Main Authors: Katja Neuhoff, Ozge Aksel Kilicarslan, Corinna Preuße, Ann-Kathrin Zaum, Heike Kölbel, Hanns Lochmüller, Ulrike Schara-Schmidt, Kiran Polavarapu, Andreas Roos, Andrea Gangfuß
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/12/12/2738
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Summary:<b>Background/Objectives</b>: X-linked dystrophinopathies are a group of neuromuscular diseases caused by pathogenic variants in the <i>DMD</i> gene (MIM *300377). Duchenne muscular dystrophy (DMD; MIM #310200) is the most common inherited muscular dystrophy. <b>Methods</b>: We screened datasets of 403 male, genetically confirmed X-linked dystrophinopathy patients and identified 13 pathogenic variants of the <i>DMD</i> gene that have not been described in the literature thus far. For all patients we provide additional data on the clinical course, genotype–phenotype correlations as well as histological datasets of nine patients. In two cases, we used RNA-Seq analyses, showing that this method can be particularly helpful in cases of deep intrinsic variants. <b>Results</b>: We were able to show, that a combination of the different datasets is helpful to counsel families and provides a better understanding of the underlying pathophysiology. <b>Conclusions</b>: Overall, we elaborated upon the persistent challenge of determining the course of disease from genetic analysis alone, rather supporting the concept of a clinical continuum of dystrophinopathies with our combined clinical, histological and molecular genetic findings.
ISSN:2227-9059