Forskning ved Københavns Universitet - Københavns Universitet


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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • 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 Bartoli
  • Gisèle Bonne
  • Pascal Laforet
  • François M Petit

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.

TidsskriftNeurology: Genetics
Udgave nummer6
Antal sider11
StatusUdgivet - dec. 2017

ID: 196371191