PT  - JOURNAL ARTICLE
AU  - Ben Yaou, Rabah
AU  - Hubert, Aurélie
AU  - Nelson, Isabelle
AU  - Dahlqvist, Julia R.
AU  - Gaist, David
AU  - Streichenberger, Nathalie
AU  - Beuvin, Maud
AU  - Krahn, Martin
AU  - Petiot, Philippe
AU  - Parisot, Frédéric
AU  - Michel, Fabrice
AU  - Malfatti, Edoardo
AU  - Romero, Norma
AU  - Carlier, Robert Yves
AU  - Eymard, Bruno
AU  - Labrune, Philippe
AU  - Duno, Morten
AU  - Krag, Thomas
AU  - Cerino, Mathieu
AU  - Bartoli, Marc
AU  - Bonne, Gisèle
AU  - Vissing, John
AU  - Laforet, Pascal
AU  - Petit, François M.
TI  - Clinical heterogeneity and phenotype/genotype findings in 5 families with <em>GYG1</em> deficiency
AID  - 10.1212/NXG.0000000000000208
DP  - 2017 Dec 01
TA  - Neurology Genetics
PG  - e208
VI  - 3
IP  - 6
4099  - http://ng.neurology.org/content/3/6/e208.short
4100  - http://ng.neurology.org/content/3/6/e208.full
SO  - Neurol Genet2017 Dec 01; 3
AB  - 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.Methods: 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.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.Conclusions: Our report extends the genetic and clinical spectrum of glycogenin-1–related myopathies to include scapuloperoneal and distal affection with glycogen accumulation.FSHD=facioscapulohumeral dystrophy; mRNA=messenger RNA; PAS=periodic acid–Schiff