POMGnT1, POMT1, and POMT2 mutations in congenital muscular dystrophies.

Alpha-dystroglycanopathies are a group of rare inherited neuromuscular disorders characterized by reduced glycosylation of alpha-dystroglycan (alpha-DG). Mutations in six genes (POMT1, POMT2, POMGNT1, FKTN, FKRP, and LARGE) have been identified in patients with alpha-dystroglycanopathies. Due to an extremely broad clinical spectrum and relatively poor phenotype-genotype correlation, diagnosis of alpha-dystroglycanopathies is difficult and requires searching for mutations gene by gene. At present, of the six proteins involved on alpha-dystroglycanopathies, the function of the gene products is only known for POMT1, POMT2, and POMGnT1, all responsible for the O-mannosylglycan biosynthesis. This chapter describes the assay protocols to diagnose patients with alpha-dystroglycanopathy by measuring glycosyltransferase activity.