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Clinical heterogeneity and phenotype/genotype findings in 5 families with GYG1 deficiency

2017; Wolters Kluwer; Volume: 3; Issue: 6 Linguagem: Inglês

10.1212/nxg.0000000000000208

2376-7839

Rabah Ben Yaou, Aurélie Hubert, Isabelle Nelson, Julia R. Dahlqvist, David Gaist, Nathalie Streichenberger, Maud Beuvin, Martin Krahn, Philippe Petiot, Frédéric Parisot, Fabrice Michel, Edoardo Malfatti, Norma B. Romero, Robert Carlier, B. Eymard, Philippe Labrune, Morten Dunø, Thomas Krag, Mathieu Cérino, Marc Bartoli, Gisèle Bonne, John Vissing, Pascal Laforêt, François Petit,

Neurogenetic and Muscular Disorders Research

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.We describe 9 patients from 5 families in whom muscle biopsies showed vacuoles with an abnormal accumulation of glycogen in muscle fibers, partially α-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.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.Our report extends the genetic and clinical spectrum of glycogenin-1-related myopathies to include scapuloperoneal and distal affection with glycogen accumulation.