2. Academic Validation
  3. Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis

Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis

  • Science. 1997 Jul 11;277(5323):228-31. doi: 10.1126/science.277.5323.228.
E D Carstea 1,  J A Morris,  K G Coleman,  S K Loftus,  D Zhang,  C Cummings,  J Gu,  M A Rosenfeld,  W J Pavan,  D B Krizman,  J Nagle,  M H Polymeropoulos,  S L Sturley,  Y A Ioannou,  M E Higgins,  M Comly,  A Cooney,  A Brown,  C R Kaneski,  E J Blanchette-Mackie,  N K Dwyer,  E B Neufeld,  T Y Chang,  L Liscum,  J F Strauss 3rd,  K Ohno,  M Zeigler,  R Carmi,  J Sokol,  D Markie,  R R O'Neill,  O P van Diggelen,  M Elleder,  M C Patterson,  R O Brady,  M T Vanier,  P G Pentchev,  D A Tagle
Affiliations

Affiliation

  • 1 National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
PMID: 9211849 DOI: 10.1126/science.277.5323.228
Abstract

Niemann-Pick type C (NP-C) disease, a fatal neurovisceral disorder, is characterized by lysosomal accumulation of low density lipoprotein (LDL)-derived Cholesterol. By positional cloning methods, a gene (NPC1) with insertion, deletion, and missense mutations has been identified in NP-C patients. Transfection of NP-C fibroblasts with wild-type NPC1 cDNA resulted in correction of their excessive lysosomal storage of LDL Cholesterol, thereby defining the critical role of NPC1 in regulation of intracellular Cholesterol trafficking. The 1278-amino acid NPC1 protein has sequence similarity to the morphogen receptor PATCHED and the putative sterol-sensing regions of SREBP cleavage-activating protein (SCAP) and 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase.

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