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

Eugene D. Carstea; Jill A. Morris; Katherine G. Coleman; Stacie K. Loftus; Dana Zhang; Christiano Cummings; Jessie Gu; Melissa A. Rosenfeld; William J. Pavan; David B. Krizman; James Nagle; Mihail H. Polymeropoulos; Stephen L. Sturley; Yiannis A. Ioannou; Maureen E. Higgins; Marcella Comly; Adele Cooney; Anthony Brown; Christine R. Kaneski; E. Joan Blanchette-Mackie; Nancy K. Dwyer; Edward B. Neufeld; Ta Yuan Chang; Laura Liscum; Jerome F. Strauss; Kousaku Ohno; Marsha Zeigler; Rivka Carmi; Jacob Sokol; David Markie; Raymond R. O'Neill; O. P. Van Diggelen; Milan Elleder; Marc C. Patterson; Roscoe O. Brady; Marie T. Vanier; Peter G. Pentchev; Danilo A. Tagle

doi:10.1126/science.277.5323.228

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

Eugene D. Carstea, Jill A. Morris, Katherine G. Coleman, Stacie K. Loftus, Dana Zhang, Christiano Cummings, Jessie Gu, Melissa A. Rosenfeld, William J. Pavan, David B. Krizman, James Nagle, Mihail H. Polymeropoulos, Stephen L. Sturley, Yiannis A. Ioannou, Maureen E. Higgins, Marcella Comly, Adele Cooney, Anthony Brown, Christine R. Kaneski, E. Joan Blanchette-MackieNancy K. Dwyer, Edward B. Neufeld, Ta Yuan Chang, Laura Liscum, Jerome F. Strauss, Kousaku Ohno, Marsha Zeigler, Rivka Carmi, Jacob Sokol, David Markie, Raymond R. O'Neill, O. P. Van Diggelen, Milan Elleder, Marc C. Patterson, Roscoe O. Brady, Marie T. Vanier, Peter G. Pentchev, Danilo A. Tagle

Ben-Gurion University of the Negev

Research output: Contribution to journal › Article › peer-review

1282 Scopus citations

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.

Original language	English
Pages (from-to)	228-231
Number of pages	4
Journal	Science
Volume	277
Issue number	5323
DOIs	https://doi.org/10.1126/science.277.5323.228
State	Published - 11 Jul 1997

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Carstea, E. D., Morris, J. A., Coleman, K. G., Loftus, S. K., Zhang, D., Cummings, C., Gu, J., Rosenfeld, M. A., Pavan, W. J., Krizman, D. B., Nagle, J., Polymeropoulos, M. H., Sturley, S. L., Ioannou, Y. A., Higgins, M. E., Comly, M., Cooney, A., Brown, A., Kaneski, C. R., ... Tagle, D. A. (1997). Niemann-Pick C1 disease gene: Homology to mediators of cholesterol homeostasis. Science, 277(5323), 228-231. https://doi.org/10.1126/science.277.5323.228

@article{6d89b51d8c7f43ecbc66e4f8126b9200,

title = "Niemann-Pick C1 disease gene: Homology to mediators of cholesterol homeostasis",

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.",

author = "Carstea, {Eugene D.} and Morris, {Jill A.} and Coleman, {Katherine G.} and Loftus, {Stacie K.} and Dana Zhang and Christiano Cummings and Jessie Gu and Rosenfeld, {Melissa A.} and Pavan, {William J.} and Krizman, {David B.} and James Nagle and Polymeropoulos, {Mihail H.} and Sturley, {Stephen L.} and Ioannou, {Yiannis A.} and Higgins, {Maureen E.} and Marcella Comly and Adele Cooney and Anthony Brown and Kaneski, {Christine R.} and Blanchette-Mackie, {E. Joan} and Dwyer, {Nancy K.} and Neufeld, {Edward B.} and Chang, {Ta Yuan} and Laura Liscum and Strauss, {Jerome F.} and Kousaku Ohno and Marsha Zeigler and Rivka Carmi and Jacob Sokol and David Markie and O'Neill, {Raymond R.} and {Van Diggelen}, {O. P.} and Milan Elleder and Patterson, {Marc C.} and Brady, {Roscoe O.} and Vanier, {Marie T.} and Pentchev, {Peter G.} and Tagle, {Danilo A.}",

year = "1997",

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day = "11",

doi = "10.1126/science.277.5323.228",

language = "English",

volume = "277",

pages = "228--231",

journal = "Science",

issn = "0036-8075",

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Carstea, ED, Morris, JA, Coleman, KG, Loftus, SK, Zhang, D, Cummings, C, Gu, J, Rosenfeld, MA, Pavan, WJ, Krizman, DB, Nagle, J, Polymeropoulos, MH, Sturley, SL, Ioannou, YA, Higgins, ME, Comly, M, Cooney, A, Brown, A, Kaneski, CR, Blanchette-Mackie, EJ, Dwyer, NK, Neufeld, EB, Chang, TY, Liscum, L, Strauss, JF, Ohno, K, Zeigler, M, Carmi, R, Sokol, J, Markie, D, O'Neill, RR, Van Diggelen, OP, Elleder, M, Patterson, MC, Brady, RO, Vanier, MT, Pentchev, PG & Tagle, DA 1997, 'Niemann-Pick C1 disease gene: Homology to mediators of cholesterol homeostasis', Science, vol. 277, no. 5323, pp. 228-231. https://doi.org/10.1126/science.277.5323.228

TY - JOUR

T1 - Niemann-Pick C1 disease gene

T2 - Homology to mediators of cholesterol homeostasis

AU - Carstea, Eugene D.

AU - Morris, Jill A.

AU - Coleman, Katherine G.

AU - Loftus, Stacie K.

AU - Zhang, Dana

AU - Cummings, Christiano

AU - Gu, Jessie

AU - Rosenfeld, Melissa A.

AU - Pavan, William J.

AU - Krizman, David B.

AU - Nagle, James

AU - Polymeropoulos, Mihail H.

AU - Sturley, Stephen L.

AU - Ioannou, Yiannis A.

AU - Higgins, Maureen E.

AU - Comly, Marcella

AU - Cooney, Adele

AU - Brown, Anthony

AU - Kaneski, Christine R.

AU - Blanchette-Mackie, E. Joan

AU - Dwyer, Nancy K.

AU - Neufeld, Edward B.

AU - Chang, Ta Yuan

AU - Liscum, Laura

AU - Strauss, Jerome F.

AU - Ohno, Kousaku

AU - Zeigler, Marsha

AU - Carmi, Rivka

AU - Sokol, Jacob

AU - Markie, David

AU - O'Neill, Raymond R.

AU - Van Diggelen, O. P.

AU - Elleder, Milan

AU - Patterson, Marc C.

AU - Brady, Roscoe O.

AU - Vanier, Marie T.

AU - Pentchev, Peter G.

AU - Tagle, Danilo A.

PY - 1997/7/11

Y1 - 1997/7/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0030863352&partnerID=8YFLogxK

U2 - 10.1126/science.277.5323.228

DO - 10.1126/science.277.5323.228

M3 - Article

AN - SCOPUS:0030863352

SN - 0036-8075

VL - 277

SP - 228

EP - 231

JO - Science

JF - Science

IS - 5323

ER -

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

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