Identification of HE1 as the Second Gene of Niemann-Pick C Disease

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-b...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2000-12, Vol.290 (5500), p.2298-2301
Main Authors: Naureckiene, Saule, David. E. Sleat, Lackland, Henry, Fensom, Anthony, Vanier, Marie T., Wattiaux, Robert, Jadot, Michel, Lobel, Peter
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Anatomy
Animals
Biological and medical sciences
Biological Transport
Brain
Carrier Proteins
Cell lines
Cell Membrane - metabolism
Cells, Cultured
CHO Cells
Cholesterol
Cholesterol - metabolism
cholesterol-binding protein
Cholesterols
chromosome 14
Coding
Cricetinae
Culture Media, Conditioned
Cultured cells
Disease
Errors of metabolism
Etiology
Exons
Fibroblasts
Fibroblasts - metabolism
Fractions
Gels
Genes
Genetic Disorders
Genetic mutation
Glycoproteins - chemistry
Glycoproteins - genetics
Glycoproteins - metabolism
Glycoproteins - pharmacology
HE1 gene
Humans
Lipid metabolism disorders
Lipidosis
Lipids (lysosomal enzyme disorders, storage diseases)
Lysosomes - metabolism
Medical sciences
Metabolic diseases
Molecular Sequence Data
Mutation
Nervous system diseases
Niemann Pick diseases
Niemann-Pick Diseases - genetics
Niemann-Pick Diseases - metabolism
Patients
Proteins
Rats
Receptor, IGF Type 2 - metabolism
Recombinant Proteins - metabolism
Recombinant Proteins - pharmacology
Transfection
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Description
Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.290.5500.2298