Journal ArticleDOI
Identification of HE1 as the Second Gene of Niemann-Pick C Disease
Saule Naureckiene,David E. Sleat,David E. Sleat,Henry Lackland,Anthony H. Fensom,Marie T. Vanier,Robert Wattiaux,Michel Jadot,Peter Lobel,Peter Lobel +9 more
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TLDR
Treatment of NP-C2 fibroblasts with exogenous recombinant HE1 protein ameliorated lysosomal accumulation of low density lipoprotein-derived cholesterol.Abstract:
Niemann-Pick type C2 disease (NP-C2) is a fatal hereditary disorder of unknown etiology characterized by defective egress of cholesterol from lysosomes. Here we show that the disease is caused by a deficiency in HE1, a ubiquitously expressed lysosomal protein identified previously as a cholesterol-binding protein. HE1 was undetectable in fibroblasts from NP-C2 patients but present in fibroblasts from unaffected controls and NP-C1 patients. Mutations in the HE1 gene, which maps to chromosome 14q24.3, were found in NP-C2 patients but not in controls. Treatment of NP-C2 fibroblasts with exogenous recombinant HE1 protein ameliorated lysosomal accumulation of low density lipoprotein-derived cholesterol.read more
Citations
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Dysphagia as a risk factor for mortality in Niemann-Pick disease type C: systematic literature review and evidence from studies with miglustat
Mark Walterfang,Yin-Hsiu Chien,Jackie Imrie,Derren Rushton,Danielle Schubiger,Marc C. Patterson +5 more
TL;DR: Findings indicate that a therapy capable of improving or stabilising swallowing function might reduce the risk of aspiration pneumonia, and could have a positive impact on patient survival, and that Miglustat, currently the only approved disease-specific therapy for NP-C in children and adults, has been shown to stabilise key neurological manifestations, including dysphagia.
Journal ArticleDOI
Lysosomal unesterified cholesterol content correlates with liver cell death in murine Niemann-Pick type C disease
TL;DR: It is suggested that the late endosomal/lysosomal content of unesterified cholesterol correlates with cell damage in NPC disease.
Journal ArticleDOI
Genetic and laboratory diagnostic approach in Niemann Pick disease type C.
TL;DR: Sequencing of NPC1 and NPC2 is currently the most universally accessible diagnostic technique in this disorder.
Journal ArticleDOI
Frontal lobe atrophy due to a mutation in the cholesterol binding protein HE1/NPC2.
Hans H. Klünemann,Milan Elleder,Wolfgang E. Kaminski,Karen Snow,Janis M. Peyser,John F. O'Brien,David G. Munoz,Gerd Schmitz,Helmfried E. Klein,William W. Pendlebury +9 more
TL;DR: This is the first description of slowly progressive Niemann–Pick disease type C without the typical lysosomal storage in bone marrow and viscera in two descendants of a group of 17th century French‐Canadians.
Journal ArticleDOI
NPC2 is expressed in human and murine liver and secreted into bile: Potential implications for body cholesterol homeostasis
Andrés D. Klein,Ludwig Amigo,Maria Jose Retamal,María Gabriela Morales,Juan Francisco Miquel,Attilio Rigotti,Silvana Zanlungo +6 more
TL;DR: NPC2 is secreted from the liver into bile and plasma, where it may have a functional role in cholesterol transport in normal and disease conditions.
References
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The Metabolic and Molecular Bases of Inherited Disease
TL;DR: In this paper, the authors present a list of disorders of MITOCHONDRIAL FUNCTION, including the following: DISORDERS OF MIOCHONDRIC FERTILITY XIX, XVI, XIX.
Journal ArticleDOI
Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue
TL;DR: The results are shown to favour the ferryl ion structure, or an isomer of this structure, for the higher oxidation state, and theHigher oxidation state may provisionally be named ferrylmyoglobin.
Journal ArticleDOI
Association of Mutations in a Lysosomal Protein with Classical Late-Infantile Neuronal Ceroid Lipofuscinosis
David E. Sleat,Robert J. Donnelly,Henry Lackland,Henry Lackland,Chang Gong Liu,Istvan Sohar,Istvan Sohar,Raju K. Pullarkat,Peter Lobel,Peter Lobel +9 more
TL;DR: In this paper, the mannose 6-phosphate modification of newly synthesized lysosomal enzymes was used as an affinity marker, and a single protein was identified that is absent in LINCL.
Journal ArticleDOI
Niemann–Pick C1 Is a Late Endosome-Resident Protein That Transiently Associates with Lysosomes and the Trans-Golgi Network
TL;DR: Characterizing the subcellular location of the NPC1 protein suggests that U18666A may inhibit the retrograde transport of NPC1 from lysosomes to late endosomes for subsequent transfer to the trans-Golgi network.
Journal Article
Genetic heterogeneity in Niemann-Pick C disease: a study using somatic cell hybridization and linkage analysis.
TL;DR: In this article, the authors conducted a study on skin fibroblast cultures from 32 unrelated Niemann-Pick C patients covering the range of known clinical and biochemical phenotypes.
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