Muscle pathology and whole-body MRI in a polyglucosan myopathy associated with a novel glycogenin-1 mutation.

Abstract

We report a 46-year-old female with late-onset skeletal myopathy affecting proximal limb muscles. Muscle biopsy revealed a polyglucosan myopathy with PAS-positive inclusions predominantly in glycogen-depleted fibers, which were demonstrated as type I fibers by ATPase staining. Whole-body magnetic imaging disclosed that the paravertebral, scapular, and pelvic girdle muscles, the anterior compartment of the arms, and the posterior compartment of the thighs were preferentially involved. Genetic analysis revealed a homozygous novel mutation in exon 6 of the glycogenin-1 gene (GYG1) (c.634C>T, p.His212Tyr). Protein analysis revealed normal levels of glycogenin-1 even before alpha-amylase digestion indicating preserved protein expression but impaired glucosylation. In vitro functional assay demonstrated that this variant impaired the autoglucosylating ability resulting in a non-functional protein. We report a glycogenin-1 related myopathy with a distinct histopathology and unique muscle imaging pattern.

• Authors: Sushan Luo, Wenhua Zhu, Dongyue Yue, Jie Lin, Yin Wang, Zhen Zhu, Wenjuan Qiu, Jiahong Lu, Carola Hedberg-Oldfors, Anders Oldfors, Chongbo Zhao
• Journal: Neuromuscular disorders : NMD (Neuromuscul Disord) Vol. 25 Issue 10 Pg. 780-5 (Oct 2015) ISSN: 1873-2364 [Electronic] England
• PMID: 26255073 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Glucans
• Glycoproteins
• glycogenin
• polyglucosan
• Glucosyltransferases

Topics

• Exons
• Female
• Glucans (metabolism)
• Glucosyltransferases (deficiency, genetics)
• Glycoproteins (deficiency, genetics)
• Humans
• Inclusion Bodies (pathology)
• Magnetic Resonance Imaging
• Middle Aged
• Muscle, Skeletal (metabolism, pathology)
• Muscular Diseases (genetics, metabolism, pathology)
• Mutation
• Whole Body Imaging