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A Prevalent Variant in PPP1R3A Impairs Glycogen Synthesis and Reduces Muscle Glycogen Content in Humans and Mice

2008; Public Library of Science; Volume: 5; Issue: 1 Linguagem: Inglês

10.1371/journal.pmed.0050027

1549-1676

David B. Savage, Lanmin Zhai, Ravikumar Balasubramanian, Cheol Soo Choi, J.E.M. Snaar, Amanda C McGuire, Sung-Eun Wou, Gema Medina‐Gómez, Sheene Kim, Cheryl B. Bock, Dyann M. Segvich, António Vidal-Puig, Nicholas J. Wareham, Gerald I. Shulman, Fredrik Karpe, Roy Taylor, Bartholomew A. Pederson, Peter J. Roach, Stephen O’Rahilly, Anna Depaoli-Roach,

Genetic Neurodegenerative Diseases

Stored glycogen is an important source of energy for skeletal muscle. Human genetic disorders primarily affecting skeletal muscle glycogen turnover are well-recognised, but rare. We previously reported that a frameshift/premature stop mutation in PPP1R3A, the gene encoding RGL, a key regulator of muscle glycogen metabolism, was present in 1.36% of participants from a population of white individuals in the UK. However, the functional implications of the mutation were not known. The objective of this study was to characterise the molecular and physiological consequences of this genetic variant.