Clinical heterogeneity and phenotype/genotype findings in 5 families with GYG1 deficiency
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
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.
I: Neurology: Genetics, Bind 3, Nr. 6, e208, 12.2017.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
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 - 2017/12
Y1 - 2017/12
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.
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 -
ID: 196371191