title: Identification of HE1 as the second gene of Niemann-Pick C disease.
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.
authors: Center for Advanced Biotechnology and Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA.
authors: S
authors: S
authors: Naureckiene
authors: D E
authors: DE
authors: Sleat
authors: H
authors: H
authors: Lackland
authors: A
authors: A
authors: Fensom
authors: M T
authors: MT
authors: Vanier
authors: R
authors: R
authors: Wattiaux
authors: M
authors: M
authors: Jadot
authors: P
authors: P
authors: Lobel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D016466:CHO Cells; D002352:Carrier Proteins; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D006224:Cricetinae; D017077:Culture Media, Conditioned; D005347:Fibroblasts / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009542:Niemann-Pick Diseases / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection; D033921:Vesicular Transport Proteins
chemical_list: D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D006023:Glycoproteins; C104585:NPC2 protein, human; D017527:Receptor, IGF Type 2; D011994:Recombinant Proteins; D033921:Vesicular Transport Proteins; D002784:Cholesterol