ArticleGenetics in medicine : official journal of the American College of Medical Genetics2021
Lysosomal cholesterol accumulation contributes to the movement phenotypes associated with NUS1 haploinsufficiency.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- DHDDS-related juvenile parkinsonism is caused by impaired lipid metabolism, glycosylation, and mitochondrial dysfunction, which can be rescued by NADmedRxiv : the preprint server for health sciences · 2026Article
- Movement Disorders in Developmental and Epileptic Encephalopathies.Movement disorders clinical practice · 2026Review
- Epilepsy Phenotypic Spectrum of NUS1-Related Disorder: A Case Series.Annals of the Child Neurology Society · 2026Article
- Meta-analysis of functional genomics studies reveals conserved cellular pathways required by viruses of pandemic concern.Access microbiology · 2026Article
- The Spectrum of Neurologic Phenotypes Associated With NUS1 Pathogenic Variants: A Comprehensive Case Series.Annals of neurology · 2025Article
- Loss of NgBR causes neuronal damage through decreasing KAT7-mediated RFX1 acetylation and FGF1 expression.Cellular and molecular life sciences : CMLS · 2025Article
- Niemann-Pick C-like Endolysosomal Dysfunction in DHDDS Patient Cells, a Congenital Disorder of Glycosylation, Can Be Treated with Miglustat.International journal of molecular sciences · 2025Article
- Heterozygous pathogenic STT3A variation leads to dominant congenital glycosylation disorders and functional validation in zebrafish.Orphanet journal of rare diseases · 2025Article
- Case Report:Frontiers in pediatrics · 2025Article
- Expanding the spectrum ofFrontiers in genetics · 2025Article
- Novel Copy Number Deletion InvolvingClinical case reports · 2025Article
- O-GlcNAcylation modulates expression and abundance of N-glycosylation machinery in an inherited glycosylation disorder.Cell reports · 2024Article
- Genomic insights into the comorbidity between type 2 diabetes and schizophrenia.Schizophrenia (Heidelberg, Germany) · 2024Article
- DHDDS and NUS1: A Converging Pathway and Common Phenotype.Movement disorders clinical practice · 2024Review
- Genomic insights into the comorbidity between type 2 diabetes and schizophrenia.medRxiv : the preprint server for health sciences · 2023Article
- Tracer metabolomics reveals the role of aldose reductase in glycosylation.Cell reports. Medicine · 2023Article
- Parkinsonism in Genetic Neurodevelopmental Disorders: A Systematic Review.Movement disorders clinical practice · 2023Review
- Perspectives on Retinal Dolichol Metabolism, and Visual Deficits in Dolichol Metabolism-Associated Inherited Disorders.Advances in experimental medicine and biology · 2023Review
- Case report: splicing effect of a novel heterozygous variant of the NUS1 gene in a child with epilepsy.Frontiers in genetics · 2023Article
- De novo DHDDS variants cause a neurodevelopmental and neurodegenerative disorder with myoclonus.Brain : a journal of neurology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeVariants in NUS1 are associated with a congenital disorder of glycosylation, developmental and epileptic encephalopathies, and are possible contributors to Parkinson disease pathogenesis. How the diverse functions of the NUS1-encoded Nogo B receptor (NgBR) relate to these different phenotypes is largely unknown. We present three patients with de novo heterozygous variants in NUS1 that cause a complex movement disorder, define pathogenic mechanisms in cells and zebrafish, and identify possible therapy.
methodsComprehensive functional studies were performed using patient fibroblasts, and a zebrafish model mimicking NUS1 haploinsufficiency.
resultsWe show that de novo NUS1 variants reduce NgBR and Niemann-Pick type C2 (NPC2) protein amount, impair dolichol biosynthesis, and cause lysosomal cholesterol accumulation. Reducing nus1 expression 50% in zebrafish embryos causes abnormal swim behaviors, cholesterol accumulation in the nervous system, and impaired turnover of lysosomal membrane proteins. Reduction of cholesterol buildup with 2-hydroxypropyl-ß-cyclodextrin significantly alleviates lysosomal proteolysis and motility defects.
conclusionOur results demonstrate that these NUS1 variants cause multiple lysosomal phenotypes in cells. We show that the movement deficits associated with nus1 reduction in zebrafish arise in part from defective efflux of cholesterol from lysosomes, suggesting that treatments targeting cholesterol accumulation could be therapeutic.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.