Description:
NIEMANN-PICK DISEASE, TYPE C1; NPC1
NPC1 GENE; NPC1
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Lysosomal Storage Diseases |
| Class |
Disorders of Lipid Metabolism |
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Cell Type
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Fibroblast
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Transformant
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Untransformed
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Race
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White
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| PDL at Freeze |
4.01 |
| Passage Frozen |
8 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
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| sphingomyelin phosphodiesterase |
According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.1.4.12; 50% activity. |
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| Gene |
NPC1 |
| Chromosomal Location |
18q11-q12 |
| Allelic Variant 1 |
607623.0010; NIEMANN-PICK DISEASE, TYPE C1 |
| Identified Mutation |
ILE1061THR; In an initial study of 25 patients with type C1 Niemann-Pick disease, Millat et al. [Am. J. Hum. Genet. 65: 1321-1329 (1999)] identified a T-to-C transition at nucleotide 3182 of the NPC1 gene that led to an ile1061-to-thr substitution (I1061T) in 3 patients. The mutation, located in exon 21, affected a putative transmembrane domain of the protein. The mutation was particularly frequent in patients with NPC from western Europe, especially France and the U.K. and in Hispanic patients whose roots were in the Upper Rio Grande valley of the U.S. Millat et al. [Am. J. Hum. Genet. 65: 1321-1329 (1999)] concluded that the I1061T mutation originated in Europe and that the high frequency in northern Rio Grande Hispanics resulted from a founder effect. |
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| Gene |
NPC1 |
| Chromosomal Location |
18q11-q12 |
| Allelic Variant 2 |
del740F-741S; NIEMANN-PICK DISEASE, TYPE C1 |
| Identified Mutation |
2215(or 2217)delTCCTTT(or CTTTTC) |
| Remarks |
Variant; 24% - 50% of normal sphingomyelinase activity; a brother died of Niemann-Pick at age 11; fibroblasts show impaired cholesterol esterification; the donor subject is a compound heterozygote; one allele carries a missense mutation C>T at nucleotide 709 (709C>T) in exon 6 of the NPC1 gene, resulting in a substitution of a serine for a proline at codon 237 [Pro237Ser (P237S)]; the second allele carries a 6 bp deletion in exon 14: 2215(or 2217)delTCCTTT(or CTTTTC) which results in the in frame deletion of 2 amino acids (740F,741S) |
| Umeda A, Fujita H, Kuronita T, Hirosako K, Himeno M, Tanaka Y, Distribution and trafficking of MPR300 is normal in cells with cholesterol accumulated in late endocytic compartments: evidence for early endosome-to-TGN trafficking of MPR300. J Lipid Res44(10):1821-32 2003 |
| PubMed ID: 12867541 |
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| Kruth HS, Ifrim I, Chang J, Addadi L, Perl-Treves D, Zhang WY, Monoclonal antibody detection of plasma membrane cholesterol microdomains responsive to cholesterol trafficking. J Lipid Res42(9):1492-500 2001 |
| PubMed ID: 11518770 |
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| Yamamoto T, Ninomiya H, Matsumoto M, Ohta Y, Nanba E, Tsutsumi Y, Yamakawa K,
Millat G, Vanier MT, Pentchev PG, Ohno K, Genotype-phenotype relationship of Niemann-Pick disease type C: a possible
correlation between clinical onset and levels of NPC1 protein in isolated skin
fibroblasts. J Med Genet37(9):707-12 2000 |
| PubMed ID: 11182931 |
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| Akaboshi S, Yano T, Miyawaki S, Ohno K, Takeshita K, A C57BL/KsJ mouse model of Niemann-Pick disease (spm) belongs to the same complementation group as the major childhood type of Niemann-Pick disease type C. Hum Genet99:350-3 1997 |
| PubMed ID: 9050921 |
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| Slotte JP, Hedstrom G, Bierman EL, Intracellular transport of cholesterol in type C Niemann-Pick fibroblasts. Biochim Biophys Acta1005:303-9 1989 |
| PubMed ID: 2804059 |
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| Pentchev PG, Comly ME, Kruth HS, Patel S, Proestel M, Weintroub H, The cholesterol storage disorder of the mutant BALB/c mouse. A primary genetic lesion closely linked to defective esterification of exogenously derived cholesterol and its relationship to human type C Niemann-Pick disease. J Biol Chem261:2772-7 1986 |
| PubMed ID: 3949747 |
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| Pentchev PG, Comly ME, Kruth HS, Vanier MT, Wenger DA, Patel S, Brady RO, A defect in cholesterol esterification in Niemann-Pick disease (type C) patients. Proc Natl Acad Sci U S A82:8247-51 1985 |
| PubMed ID: 3865225 |
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| Sakuragawa N, Sato M, Yoshida Y, Kamo I, Arima M, Satoyoshi E, Effects of dimethylsulfoxide on sphingomyelinase in cultured human fibroblasts and correction of sphingomyelinase deficiency in fibroblasts from Niemann-Pick patients. Biochem Biophys Res Commun126:756-62 1985 |
| PubMed ID: 2983689 |
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| Maziere JC, Maziere C, Mora L, Routier JD, Polonovski J, In situ degradation of sphingomyelin by cultured normal fibroblasts and fibroblasts from patients with Niemann-Pick disease type A and C. Biochem Biophys Res Commun108:1101-6 1982 |
| PubMed ID: 7181884 |
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| Besley GT, Hoogeboom AJ, Hoogeveen A, Kleijer WJ, Galjaard H, Somatic cell hybridisation studies showing different gene mutations in Niemann-Pick variants. Hum Genet54:409-12 1980 |
| PubMed ID: 6249719 |
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| Besley GT, Diagnosis of Niemann-Pick disease using a simple and sensitive fluorimetric assay of sphingomyelinase activity. Clin Chim Acta90:269-78 1978 |
| PubMed ID: 31994 |
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| Besley GT, Sphingomyelinase defect in Niemann-Pick disease, type C, fibroblasts. FEBS Lett80:71-4 1977 |
| PubMed ID: 19295 |
| Passage Frozen |
8 |
| Split Ratio |
1:2 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
AMBIENT |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Supplement |
- |
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