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

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 Romero, Robert Yves Carlier, Bruno Eymard, Philippe Labrune, Morten Duno, Thomas Krag, Mathieu Cerino, Marc BartoliGisèle Bonne, John Vissing, Pascal Laforet, François M Petit

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Abstract

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.

Original languageEnglish
Article numbere208
JournalNeurology: Genetics
Volume3
Issue number6
Number of pages10
ISSN2376-7839
DOIs
Publication statusPublished - 2017

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Muscles
Mutation
Exome
Muscular Diseases
Vacuoles
Proteins
glycogenin
Enzymes

Keywords

  • Journal Article

Cite this

Ben Yaou, R., Hubert, A., Nelson, I., Dahlqvist, J. R., Gaist, D., Streichenberger, N., ... Petit, F. M. (2017). Clinical heterogeneity and phenotype/genotype findings in 5 families with GYG1 deficiency. Neurology: Genetics, 3(6), [e208]. https://doi.org/10.1212/NXG.0000000000000208
Ben Yaou, Rabah ; Hubert, Aurélie ; Nelson, Isabelle ; Dahlqvist, Julia R ; Gaist, David ; Streichenberger, Nathalie ; Beuvin, Maud ; Krahn, Martin ; Petiot, Philippe ; Parisot, Frédéric ; Michel, Fabrice ; Malfatti, Edoardo ; Romero, Norma ; Carlier, Robert Yves ; Eymard, Bruno ; Labrune, Philippe ; Duno, Morten ; Krag, Thomas ; Cerino, Mathieu ; Bartoli, Marc ; Bonne, Gisèle ; Vissing, John ; Laforet, Pascal ; Petit, François M. / Clinical heterogeneity and phenotype/genotype findings in 5 families with GYG1 deficiency. In: Neurology: Genetics. 2017 ; Vol. 3, No. 6.
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abstract = "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.",
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Ben Yaou, R, Hubert, A, Nelson, I, Dahlqvist, JR, Gaist, D, Streichenberger, N, Beuvin, M, Krahn, M, Petiot, P, Parisot, F, Michel, F, Malfatti, E, Romero, N, Carlier, RY, Eymard, B, Labrune, P, Duno, M, Krag, T, Cerino, M, Bartoli, M, Bonne, G, Vissing, J, Laforet, P & Petit, FM 2017, 'Clinical heterogeneity and phenotype/genotype findings in 5 families with GYG1 deficiency', Neurology: Genetics, vol. 3, no. 6, e208. https://doi.org/10.1212/NXG.0000000000000208

Clinical heterogeneity and phenotype/genotype findings in 5 families with GYG1 deficiency. / Ben Yaou, Rabah; Hubert, Aurélie; Nelson, Isabelle; Dahlqvist, Julia R; Gaist, David; Streichenberger, Nathalie; Beuvin, Maud; Krahn, Martin; Petiot, Philippe; Parisot, Frédéric; Michel, Fabrice; Malfatti, Edoardo; Romero, Norma; Carlier, Robert Yves; Eymard, Bruno; Labrune, Philippe; Duno, Morten; Krag, Thomas; Cerino, Mathieu; Bartoli, Marc; Bonne, Gisèle; Vissing, John; Laforet, Pascal; Petit, François M.

In: Neurology: Genetics, Vol. 3, No. 6, e208, 2017.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Clinical heterogeneity and phenotype/genotype findings in 5 families with GYG1 deficiency

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

PY - 2017

Y1 - 2017

N2 - 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.

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.

KW - Journal Article

U2 - 10.1212/NXG.0000000000000208

DO - 10.1212/NXG.0000000000000208

M3 - Journal article

C2 - 29264399

VL - 3

JO - Neurology: Genetics

JF - Neurology: Genetics

SN - 2376-7839

IS - 6

M1 - e208

ER -