Journal
NEUROLOGY-GENETICS
Volume 3, Issue 6, Pages -Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/NXG.0000000000000208
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Funding
- GIS Maladies Rares Plateforme Mutations
- French Glycogenosis Association
- CURE-CMD Translational Award
- Danish Cancer Society
- Danish Medical Research Council
- AP Moller Foundations
- University of Copenhagen
- Augustinus Foundation
- Research Committee of the National Hospital
- Danielsen Foundation
- Sanofi Genzyme
- Valerion Therapeutics
- Association Institut de Myologie (AIM)
- Novo foundation
- European Community Seventh Framework Program
- Lundbeck Foundation
- INSEAM
- Association Francaise contre les myopathies (AFM)
- Sanofi/Genzyme
- Alexion Pharmaceuticals
- Ultragenyx Pharmaceuticals
- AFM-TELETHON
- Santhera Pharmaceuticals
- aTyr Pharma
- ANR French-German grant (ANR-BMBF)
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Objective: To describe the variability of muscle symptoms in patients carrying mutations in the GYG1 gene, encoding glycogenin-1, an enzyme involved in the biosynthesis of glycogen, and to discuss genotype-phenotype relations.& para;& para;Methods: We describe 9 patients from 5 families in whom muscle biopsies showed vacuoles with an abnormal accumulation of glycogen in muscle fibers, partially alpha-amylase resistant suggesting polyglucosan bodies. The patients had either progressive early-onset limb-girdle weakness or late-onset distal or scapuloperoneal muscle affection as shown by muscle imaging. No clear definite cardiac disease was found. Histologic and protein analysis investigations were performed on muscle.& para;& para;Results: Genetic analyses by direct or exome sequencing of the GYG1 gene revealed 6 different GYG1 mutations. Four of the mutations were novel. They were compound heterozygous in 3 families and homozygous in 2. Protein analysis revealed either the absence of glycogenin-1 or reduced glycogenin-1 expression with impaired glucosylation.& para;& para;Conclusions: Our report extends the genetic and clinical spectrum of glycogenin-1-related myopathies to include scapuloperoneal and distal affection with glycogen accumulation.
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