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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Molecular characterization before cell line submission to CCR
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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 |
4.18 |
| Passage Frozen |
17 |
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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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| 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 |
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. |
| Remarks |
Clinically affected; diagnosed at 25 year 1 month; died at 33 year; walked at 14.5 months; clumsy; learning difficulties; ataxia beginning at 14 year; wheel chair bound at time of death; dysarthria beginning at 17 year; dysphagia beginning at 19 year; gastrostomy beginning at age 30 year; respiratory dysfunction beginning at age 31 year; major depression beginning at age 25 year; sleeping problems beginning at age 22 year; fibroblasts showed 29 pmol CE/mg protein/6 hr activity in a cholesterol esterification assay [normal mean was 1855 +/- 1327 pmol CE/mg protein/6 hr, see Park et al. Hum Mut 22:313-325 (2003)]; fibroblasts were scored as npc-like in a filipin staining assay (see Park et al., 2003); a complementation test showed that the cells were type 1 (see Park et al., 2003); the donor subject is homozygous at the NPC1 gene locus: both alleles carry a substitution (T>C) at nucleotide 3182 (c.3182T>C) in exon 21, resulting in a missense mutation at codon 1061 [I1061T (Ile1061Thr)]; the subject also carries the following polymorphism in the NPC1 gene: homozygous substitution (T>C) at nucleotide 387 (c.387T>C) resulting in a silent mutation (Y>Y) at codon 129 [Y129Y, (Tyr129Tyr)]; the first nucleotide of the initiating Met codon is numbered +1. This fibroblast is a characteristically poor grower and will only be shipped frozen; requires particular care during growth; the recommended seeding density is 15,000 to 20,000 cells per cm2. |
| Kataura T, Sedlackova L, Sun C, Kocak G, Wilson N, Banks P, Hayat F, Trushin S, Trushina E, Maddocks ODK, Oblong JE, Miwa S, Imoto M, Saiki S, Erskine D, Migaud ME, Sarkar S, Korolchuk VI, Targeting the autophagy-NAD axis protects against cell death in Niemann-Pick type C1 disease models Cell death & disease15:382 2024 |
| PubMed ID: 38821960 |
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| Pugach EK, Feltes M, Kaufman RJ, Ory DS, Bang AG, High-content screen for modifiers of Niemann-Pick type C disease in patient cells Human molecular genetics27:2101-2112 2017 |
| PubMed ID: 29659804 |
| Passage Frozen |
17 |
| Split Ratio |
1:2 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
3% |
| Medium |
Eagles Minimum Essential Medium with Earle's salts:Dulbecco's modified MEM with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Supplement |
- |
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