Title | NGLY1 mutation causes neuromotor impairment, intellectual disability, and neuropathy. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Çağlayan, AOkay, Comu, S, Baranoski, JF, Parman, Y, Kaymakçalan, H, Akgümüş, GTuğce, Caglar, C, Dölen, D, Erson-Omay, EZeynep, Harmanci, ASerin, Mishra-Gorur, K, Freeze, HH, Yasuno, K, Bilguvar, K, Günel, M |
Journal | Eur J Med Genet |
Volume | 58 |
Issue | 1 |
Pagination | 39-43 |
Date Published | 2015 Jan |
ISSN | 1878-0849 |
Keywords | Abnormalities, Multiple, Adolescent, Child, Corneal Opacity, Developmental Disabilities, Female, Frameshift Mutation, Genotype, Humans, Intellectual Disability, Male, Movement Disorders, Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase, Peripheral Nervous System Diseases |
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. |
DOI | 10.1016/j.ejmg.2014.08.008 |
Alternate Journal | Eur J Med Genet |
PubMed ID | 25220016 |
PubMed Central ID | PMC4804755 |
Grant List | RC2 NS070477 / NS / NINDS NIH HHS / United States U54HG006504 / HG / NHGRI NIH HHS / United States U54 HG006504 / HG / NHGRI NIH HHS / United States RC2NS070477 / NS / NINDS NIH HHS / United States R01 MH103616 / MH / NIMH NIH HHS / United States |