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

NGLY1 mutation causes neuromotor impairment, intellectual disability, and neuropathy.

Author information

1
Departments of Neurosurgery, Neurobiology and Genetics, Yale Program in Neurogenetics, Yale School of Medicine, New Haven 06510, CT, USA. Electronic address: okaycaglayan@yahoo.com.
2
Department of Pediatrics, Division of Pediatric Neurology, Sisli, Memorial Hospital, Istanbul 34385, Turkey.
3
Departments of Neurosurgery, Neurobiology and Genetics, Yale Program in Neurogenetics, Yale School of Medicine, New Haven 06510, CT, USA.
4
Department of Neurology, Istanbul University, Faculty of Medicine, Istanbul 34098, Turkey.
5
Department of Genetics and Bioinformatics, Faculty of Engineering, Bahcesehir University, Istanbul 34353, Turkey.
6
Genetic Disease Program, Sanford-Burnham Medical Research Institute, La Jolla 92037, CA, USA.
7
Departments of Neurosurgery, Neurobiology and Genetics, Yale Program in Neurogenetics, Yale School of Medicine, New Haven 06510, CT, USA. Electronic address: murat.gunel@yale.edu.

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

PMID:
25220016
PMCID:
PMC4804755
DOI:
10.1016/j.ejmg.2014.08.008
[Indexed for MEDLINE]
Free PMC Article

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