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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Family Member
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1
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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 |
4.23 |
| Passage Frozen |
19 |
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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 |
R404W; NIEMANN-PICK DISEASE, TYPE C1 |
| Identified Mutation |
ARG404TRP |
| Remarks |
Clinically affected; fibroblasts showed 26 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 of the type 1 complementation group (see Park et al., 2003); the donor subject is a compound heterozygote at the NPC1 gene locus: allele 1 carries a substitution (T>C) at nucleotide 3182 (c.3182T>C) in exon 21, resulting in a missense mutation at codon 1061 [I1061T (ILE1061THR)]; allele 2 carries a substitution (C>T) at nucleotide 1210 (c.1210C>T) in exon 8, resulting in a missense mutation at codon 404 [R404W (ARG404TRP)]; the first nucleotide of the initiating Met codon is numbered +1. |
| Furtado D, Cortez-Jugo C, Hung YH, Bush AI, Caruso F, mRNA Treatment Rescues Niemann-Pick Disease Type C1 in Patient Fibroblasts Molecular pharmaceutics19:3987-3999 2022 |
| PubMed ID: 36125338 |
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| Park WD, O'Brien JF, Lundquist PA, Kraft DL, Vockley CW, Karnes PS, Patterson MC, Snow K, Identification of 58 novel mutations in Niemann-Pick disease type C: Correlation with biochemical phenotype and importance of PTC1-like domains in NPC1. Hum Mutat22(4):313-25 2003 |
| PubMed ID: 12955717 |
| Passage Frozen |
19 |
| 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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