Whole exome sequencing in foetal akinesia expands the genotype-phenotype spectrum of GBE1 glycogen storage disease mutations

Neuromuscul Disord. 2013 Feb;23(2):165-9. doi: 10.1016/j.nmd.2012.11.005. Epub 2012 Dec 3.


The clinically and genetically heterogenous foetal akinesias have low rates of genetic diagnosis. Exome sequencing of two siblings with phenotypic lethal multiple pterygium syndrome identified compound heterozygozity for a known splice site mutation (c.691+2T>C) and a novel missense mutation (c.956A>G; p.His319Arg) in glycogen branching enzyme 1 (GBE1). GBE1 mutations cause glycogen storage disease IV (GSD IV), including a severe foetal akinesia sub-phenotype. Re-investigating the muscle pathology identified storage material, consistent with GSD IV, which was confirmed biochemically. This study highlights the power of exome sequencing in genetically heterogeneous diseases and adds multiple pterygium syndrome to the phenotypic spectrum of GBE1 mutation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / diagnosis
  • Abnormalities, Multiple / genetics*
  • Amino Acid Sequence
  • Arthrogryposis / diagnosis
  • Arthrogryposis / genetics*
  • Australia
  • Biopsy
  • Exome / genetics*
  • Fatal Outcome
  • Female
  • Genotype*
  • Glycogen Debranching Enzyme System / genetics*
  • Glycogen Storage Disease / diagnosis
  • Glycogen Storage Disease / genetics*
  • Humans
  • Infant, Newborn
  • Male
  • Malignant Hyperthermia / diagnosis
  • Malignant Hyperthermia / genetics*
  • Molecular Sequence Data
  • Muscle, Skeletal / pathology
  • Mutation, Missense / genetics*
  • Pedigree
  • Phenotype*
  • Skin Abnormalities / diagnosis
  • Skin Abnormalities / genetics*


  • Glycogen Debranching Enzyme System
  • GBE1 protein, human

Supplementary concepts

  • Multiple pterygium syndrome
  • Pena Shokeir syndrome, type 1