NGLY1 mutation causes neuromotor impairment, intellectual disability, and neuropathy

Eur J Med Genet. 2015 Jan;58(1):39-43. doi: 10.1016/j.ejmg.2014.08.008. Epub 2014 Sep 9.

Abstract

N-glycanase 1 (NGLY1) is a conserved enzyme that is responsible for the deglycosylation of misfolded N-glycosylated proteins in the cytoplasm prior to their proteasome-mediated degradation. Disruption of this degradation process has been associated with various neurologic diseases including amyotrophic lateral sclerosis and Parkinson's disease. Here, we describe two siblings with neuromotor impairment, apparent intellectual disability, corneal opacities, and neuropathy who were found to possess a novel homozygous frame-shift mutation due to a 4 base pair deletion in NGLY1 (c.1533_1536delTCAA, p.Asn511LysfsX51). We hypothesize that this mutation likely limits the capability of neuronal cells to respond to stress due to accumulation of misfolded proteins, thereby impairing their survival and resulting in progressive loss of neurological function.

Keywords: Deglycosylation; Intellectual disability; NGLY1; Neuromotor defect; Whole-exome sequencing.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics
  • Adolescent
  • Child
  • Corneal Opacity / genetics
  • Developmental Disabilities / genetics*
  • Female
  • Frameshift Mutation
  • Genotype
  • Humans
  • Intellectual Disability / genetics*
  • Male
  • Movement Disorders / genetics*
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / genetics*
  • Peripheral Nervous System Diseases / genetics*

Substances

  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase