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Science 22 December 2000:
Vol. 290. no. 5500, pp. 2298 - 2301
DOI: 10.1126/science.290.5500.2298
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Reports

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

Saule Naureckiene,1 David. E. Sleat,12 Henry Lackland,1 Anthony Fensom,3 Marie T. Vanier,4 Robert Wattiaux,5 Michel Jadot,5 Peter Lobel12*

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.

1 Center for Advanced Biotechnology and Medicine,
2 Department of Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA.
3 Division of Medical and Molecular Genetics, the Guy's, King's and St. Thomas' School of Medicine, Guy's Hospital, London, UK.
4 INSERM 189, Lyon-Sud Medical School, Oullins, France, and Fondation Gillet-Mérieux, Lyon-Sud Hospital, Pierre-Bénite, France.
5 Laboratory of Physiological Chemistry, Facultés Universitaires Notre-Dame de la Paix, B-5000 Namur, Belgium.
*   To whom correspondence should be addressed. E-mail: lobel{at}cabm.rutgers.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)