Report: Fourth International Workshop for Glycosylation Defects in Muscular Dystrophies

The Fourth International Workshop for Glycosylation Defects in Muscular Dystrophies took place on April 1617, 2015 at the Fairfield Inn and Suites Charlotte Uptown, Charlotte, North Carolina. The workshop was hosted by the McColl-Lockwood Laboratory for Muscular Dystrophy Research, and sponsored by the Carolinas HealthCare Foundation, the Muscular Dystrophy Association (MDA), funds raised by “Riding 4 Research” and generous support from the McColl and Lockwood families. Clinicians and scientists from the US, UK, Germany and Japan presented a total of 21 talks spread out over 2 days. The workshop was divided into three sessions: Session A focused on the current status of the development of animal models for diseases caused by defects in muscle-protein glycosylation, on our current understanding of such glycosylation and on the mechanisms that lead to disease. Session B focused on preclinical therapeutics, in particular on AAVand drug-based therapies. Session C covered the clinical management of muscular dystrophies and endpoint evaluation. are caused by aberrant glycosylation of α-DG, which together with β-DG forms dystroglycan. This dimer is part of the dystrophinglycoprotein complex (DGC), an entity that maintains stability of the muscle membrane by binding to the extracellular matrix (ECM), and the glycosylation of α-DG is crucial for this interaction. This “functional modification” of α-DG involves various putative and known glycosyltransferases, of which 18 have been identified: glycosyltransferase-like-protein (LARGE), fukutin-related protein (FKRP), fukutin, protein O-mannosyltransferase 1 and 2 (POMT1/2), protein O-mannose beta-1,2-N-acetylglucosaminyltransferase 1(POMGnT), isoprenoid synthase domain-containing protein (ISPD), GTDC2, beta-2-Polypeptide N-Acetylgalactosaminyltransferase (β2GALNT2), protein-O-mannose kinase (SGK196), Beta-1,4-Glucuronyltransferase 1 (β3GNT1), transmembrane protein (TMEM5), dolichol kinase (DOLK), GDP-Mannose Pyrophosphorylase B (GMPPB), Dentin Matrix Acidic Phosphoprotein (DMP1 DMP2, and DMP3) (1-12). In a majority of cases, the biochemical function has been elucidated; the exceptions are FKRP and Fukutin. Dystroglycanopathies manifest as a spectrum of phenotypes, ranging from mild limb girdle muscular dystrophy 2I (LGMD2I, characterized by later onset and near normal life span) to severe congenital muscular dystrophies such as WalkerWarburg syndrome (WWS) and muscle-brain-eye disease (MBE). The most common form of dystroglycanopathy is limb-girdle muscular dystrophy 2I (LGMD2I), which is associated with mutations in FKRP. Despite significant advancements in understanding the cause of these diseases and the characteristic defects in α-DG glycosylation, it has not Citation: Blaeser A, Harper A, Campbell K, Lu QL (2016) Report: Fourth International Workshop for Glycosylation Defects in Muscular Dystrophies. J Genet Syndr Gene Ther 7: 286. doi:10.4172/2157-7412.1000286