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</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.