title: 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.affiliation: Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Sushan
authors.initials: S
authors.lastname: Luo
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China; Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Dongyue
authors.initials: D
authors.lastname: Yue
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Neuropathology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Radiology, Children's Hospital of Shanghai, Jiaotong University, Shanghai, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Pediatric Endocrinology, Genetic and Metabolic Diseases, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Qiu
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Jiahong
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Pathology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Carola
authors.initials: C
authors.lastname: Hedberg-Oldfors
authors.affiliation: Department of Pathology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden. Electronic address: anders.oldfors@gu.se.
authors.forename: Anders
authors.initials: A
authors.lastname: Oldfors
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China; Department of Neurology, Jing'an District Center Hospital of Shanghai, Shanghai, China. Electronic address: zhao_chongbo@fudan.edu.cn.
authors.forename: Chongbo
authors.initials: C
authors.lastname: Zhao
mesh_terms: D005091:Exons; D005260:Female; D005936:Glucans / Q000378:metabolism*; D005964:Glucosyltransferases / Q000172:deficiency / Q000235:genetics*; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009154:Mutation; D051598:Whole Body Imaging
chemical_list: D005936:Glucans; D006023:Glycoproteins; C051887:glycogenin; C083094:polyglucosan; D005964:Glucosyltransferases
keywords: GYG1 gene; Glycogenin-1; Late-onset myopathy; Polyglucosan myopathy; Whole-body imaging