Niemann-Pick disease type C
Abstract
Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral lipid storage with a wide spectrum of clinical phenotypes. At the cellular level, the disorder is characterized by accumulation of unesterified cholesterol and glycolipids in the lysosomal/late endosomal system. Approximatively 95% of patients have mutations in the NPC1 gene (mapped at 18q11) which encodes a large membrane glycoprotein primarily located to late endosomes. The remainder have mutations in the NPC2 gene (mapped at 14q24.3) which encodes a small soluble lysosomal protein with cholesterol-binding properties. The identical biochemical patterns observed in NPC1 and NPC2 mutants suggest that the two proteins function in a coordinate fashion. Identification of mutations revealed a complex picture of molecular heterogeneity, allowing genotype - phenotype correlations for both genes and providing insights into structure - function relationships for the NPC1 protein. Although a whole body of evidence suggests that the NPC1 and NPC2 proteins are involved in the cellular postlysosomal/late endosomal transport of cholesterol, glycolipids and other cargo, their precise functions and relationship remain unclear and are currently the subject of intense investigation. These studies, conducted in various models, should ultimately lead to a better understanding of the pathophysiology of NPC and new therapeutic approaches.
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Patients with the same NPC mutation show very different pathological symptoms.
“Interestingly, patients with the same mutation show very different pathological symptoms [36,38].”
From Loss of Mevalonate/Cholesterol Homeostasis in the Brain: A Focus on Autism Spectrum Disorder and Rett Syndrome (2019) · cites this paper as [36]
Niemann-Pick type C disease (NPC) is characterized by intracellular accumulation of unesterified cholesterol and glycolipids in the endosomal/lysosomal system.
“The pathology is characterized by intracellular accumulation of unesterified cholesterol and glycolipids in the endosomal/lysosomal system [36].”
From Loss of Mevalonate/Cholesterol Homeostasis in the Brain: A Focus on Autism Spectrum Disorder and Rett Syndrome (2019) · cites this paper as [36]
Cites
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“Several proteins residing in the endosomal–lysosomal system, NPC1, NPC2, but also MLN 64 and MENTHO (97, 98), may be sequentially or alternatively involved in the facilitation of cellular cholesterol movements (19).”
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- Authors
- Vanier, M., & Millat, G.
- Affiliations
- Inserm (FR)
- ORCID
- Millat, G
- Venue
- Clinical Genetics
- Publisher
- Wiley
- Published
- 2003-09-15
- Volume
- 64
- Issue
- 4
- Pages
- 269-281
- ISSN
- 0009-9163 (ISSN-L)
- 1399-0004
- OpenAlex
- W3024300525
- Cited by
- 578
- References
- 1
- Citations by year
- 2026: 3 · 2025: 15 · 2024: 9 · 2023: 23 · 2022: 18 · 2021: 25 · 2020: 21 · 2019: 32 · 2018: 24 · 2017: 25 · 2016: 23 · 2015: 27 · 2014: 37 · 2013: 32 · 2012: 37
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Topics
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
- Health Sciences › Medicine › Pathology and Forensic Medicine › Biomedical Research and Pathophysiology
- Keywords
- Niemann-Pick disease type C, NPC1 gene, NPC2 gene, unesterified cholesterol accumulation, glycolipid accumulation, late endosomes, lysosomal storage disease, autosomal recessive inheritance, genotype-phenotype correlation, cholesterol transport
- MeSH terms
- Niemann-Pick C1 Protein, Carrier Proteins, Cholesterol, Chromosomes, Human, Pair 14, Chromosomes, Human, Pair 18, Genes, Recessive, Glycolipids, Glycoproteins, Humans, Membrane Glycoproteins, Models, Molecular, Mutation, Niemann-Pick Diseases, Phenotype, Structure-Activity Relationship, Vesicular Transport Proteins, Intracellular Signaling Peptides and Proteins
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