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
  • 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.