Late-onset polyglucosan body myopathy in five patients with a homozygous mutation in GYG1

•Polyglucosan myopathies are due to GBE, PFK deficiencies and to mutations in RBCK1, and GYG-1.•GYG1-splice site mutation causes polyglucosan myopathy and typical MRI muscle lesions.•We have identified a single intronic GYG-1 mutation in all five Sardinian patients.

Five Sardinian patients presented in their 5th or 6th decade with progressive limb girdle muscle weakness but their muscle biopsies showed vacuolar myopathy. The more or less abundant subsarcolemmal and intermyofibrillar vacuoles showed intense, partially α-amylase resistant, PAS-positive deposits consistent with polyglucosan. The recent description of late-onset polyglucosan myopathy has prompted us to find new genetic defects in the gene (GYG1) encoding glycogenin-1, the crucial primer enzyme of glycogen synthesis in muscle.We found a single homozygous intronic mutation harbored by five patients, who, except for two siblings, appear to be unrelated but all five live in central or south Sardinian villages.