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Lookup NU author(s): Professor Giorgio TascaORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2019 Endocrine Society 2019.Context: Glycogenin is considered to be an essential primer for glycogen biosynthesis. Nevertheless, patients with glycogenin-1 deficiency due to biallelic GYG1 (NM-004130.3) mutations can store glycogen in muscle. Glycogenin-2 has been suggested as an alternative primer for glycogen synthesis in patients with glycogenin-1 deficiency. Objective: The objective of this article is to investigate the importance of glycogenin-1 and glycogenin-2 for glycogen synthesis in skeletal and cardiac muscle. Design, Setting, and Patients: Glycogenin-1 and glycogenin-2 expression was analyzed by Western blot, mass spectrometry, and immunohistochemistry in liver, heart, and skeletal muscle from controls and in skeletal and cardiac muscle from patients with glycogenin-1 deficiency. Results: Glycogenin-1 and glycogenin-2 both were found to be expressed in the liver, but only glycogenin-1 was identified in heart and skeletal muscle from controls. In patients with truncating GYG1 mutations, neither glycogenin-1 nor glycogenin-2 was expressed in skeletal muscle. However, nonfunctional glycogenin-1 but not glycogenin-2 was identified in cardiac muscle from patients with cardiomyopathy due to GYG1 missense mutations. By immunohistochemistry, the mutated glycogenin-1 colocalized with the storage of glycogen and polyglucosan in cardiomyocytes. Conclusions: Glycogen can be synthesized in the absence of glycogenin, and glycogenin-1 deficiency is not compensated for by upregulation of functional glycogenin-2. Absence of glycogenin-1 leads to the focal accumulation of glycogen and polyglucosan in skeletal muscle fibers. Expression of mutated glycogenin-1 in the heart is deleterious, and it leads to storage of abnormal glycogen and cardiomyopathy.
Author(s): Visuttijai K, Hedberg-Oldfors C, Thomsen C, Glamuzina E, Kornblum C, Tasca G, Hernandez-Lain A, Sandstedt J, Dellgren G, Roach P, Oldfors A
Publication type: Article
Publication status: Published
Journal: Journal of Clinical Endocrinology and Metabolism
Year: 2020
Volume: 105
Issue: 2
Pages: 557–566
Print publication date: 01/02/2020
Online publication date: 19/10/2019
Acceptance date: 02/10/2019
Date deposited: 27/02/2023
ISSN (print): 0021-972X
ISSN (electronic): 1945-7197
Publisher: Endocrine Society
URL: https://doi.org/10.1210/clinem/dgz075
DOI: 10.1210/clinem/dgz075
PubMed id: 31628455
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