Author:
Chen Songjie,Wang Guangwen,Shen Xiaotao,Hornburg Daniel,Rego Shannon,Hoffman Rene,Nevins Stephanie,Cheng Xun,Snyder Michael
Abstract
AbstractNGLY1 (N-glycanase 1) deficiency is a rare congenital recessive disorder of protein deglycosylation unaddressed by the current standard of care. Using combined metabolomics and proteomics profiling, we show that NGLY1 deficiency activates the immune response and disturbs lipid metabolism, biogenic amine synthesis, and glutathione metabolism. These alterations were also observed in NGLY1 deficient patient-derived induced pluripotent stem cells (iPSCs) and differentiated neural progenitor cells (NPCs), which serve as personalized cellular models of the disease. These findings provide molecular insight into the pathophysiology of NGLY1 deficiency and suggest potential therapeutic strategies.
Publisher
Cold Spring Harbor Laboratory
Reference140 articles.
1. Mutations in NGLY1 cause an inherited disorder of the endoplasmic reticulum–associated degradation pathway
2. Prospective phenotyping of NGLY1-CDDG, the first congenital disorder of deglycosylation
3. Novel NGLY1 gene variants in Chinese children with global developmental delay, microcephaly, hypotonia, hypertransaminasemia, alacrimia, and feeding difficulty;J Hum Genet,2020
4. NGLY1 Deficiency: A Rare Newly Described Condition with a Typical Presentation;Life (Basel),2021
5. NGLY1 deficiency: Novel patient, review of the literature and diagnostic algorithm;JIMD Rep,2020
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