Proteomic studies in VWA1-related neuromyopathy allowed new pathophysiological insights and the definition of blood biomarkers

Pathogenic bi-allelic variants in VWA1, encoding Von Willebrand Factor A domain containing 1 protein localized to the extracellular matrix were recently linked to the manifestation of a neuromuscular disorder with manifestation in child- or adulthood. Myopathological and neurophysiological findings in patients are indicative of combined neurogenic and myopathic pathology classified as neuromyopathy presenting with muscle weakness (predominantly of the lower limbs) as a key clinical feature. Given that pathophysiological processes are still incompletely understood and biomarkers for this disease are still missing, we aimed to identify blood biomarkers of pathophysiological relevance. To this end, white blood cells (WBC) and plasma derived from six patients from two unrelated families were investigated by mass spectrometry. Four proteins, BET1, HNRNPDL, NEFM and PHGDH, known to be involved in neurological diseases and dysregulated in WBC were further confirmed by immunostaining studies on muscle biopsies derived from two VWA1-patients.