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Background: Duchenne Muscular Dystrophy (DMD) is a severe, progressive, neuromuscular disorder of childhood. While a number of serum factors have been identified as potential biomarkers of DMD, none, as yet, are proteins within the dystrophin-associated glycoprotein (DAG) complex., Objective: We have developed an immobilized serum ELISA assay to measure the expression of a constitutively cleaved and secreted component of the DAG complex, the N-terminal domain of α dystroglycan (αDG-N), and assayed relative expression in serum from muscular dystrophy patients and normal controls., Methods: ELISAs of immobilized patient or mouse serum and Western blots were used to assess αDG-N expression., Results: Immobilization of diluted serum on ELISA plates was important for this assay, as methods to measure serum αDG-N in solution were less robust. αDG-N ELISA signals were significantly reduced in DMD serum (27±3% decrease, n = 9, p < 0.001) relative to serum from otherwise normal controls (n = 38), and calculated serum αDG-N concentrations were reduced in DMD relative to normal (p < 0.01) and Becker Muscular Dystrophy (n = 11, p < 0.05) patient serum. By contrast, ELISA signals from patients with Inclusion Body Myositis were not different than normal (4±3% decrease, n = 8, p = 0.99). αDG-N serum signals were also significantly reduced in utrophin-deficient mdx mice as compared to mdx and wild type mice., Conclusions: Our results are the first demonstration of a component of the DAG complex as a potential serum biomarker in DMD. Such a serum measure could be further developed as a tool to help reflect overall muscle DAG complex expression or stability.

We describe two unrelated girls with congenital muscular dystrophy associated with alpha-dystroglycan deficit with no identified genetic defect, both presenting severe drug-resistant epilepsy with predominant myoclonic seizures and an unusual similar EEG pattern. Severe epilepsy has been unusually described in patients with congenital muscular dystrophies, mainly associated with Walker-Warburg, Fukuyama and muscle-eye-brain diseases. [Published with video sequences].