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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| 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 |
P543L; NIEMANN-PICK DISEASE, TYPE C1 |
| Identified Mutation |
PRO543LEU |
| Remarks |
Clinically affected; the donor subject is a compound heterozygote at the NPC1 gene locus: allele 1 carries a substitution (T>C) at nucleotide 3182 (3182T>C) in exon 21, resulting in a missense mutation at codon 1061 [I1061T (ILE1061THR)]; allele 2 carries a substitution (C>T) at nucleotide 1628 (c.1628C>T) in exon 10, resulting in a missense mutation at codon 543 [P543L (PRO543LEU)]; the subject also carries the following polymorphisms: T>C at nucleotide 387 (c.387T>C) resulting in no change (Y>Y) at codon 129 [Y129Y, (TYR129TYR)]; A>G at nucleotide 644 (c.644A>G) resulting in the substitution of arginine for histidine (H>R) at codon 215 [H215R (HIS215ARG)]; A>G at nucleotide IVS11+60 (IVS11+60A>G) resulting in no change in the predicted amino acid sequence; C>T at nucleotide 2793 (c.2793C>T) resulting in no change (N>N) at codon 931 [N931N (ASN931ASN)]; T>C at nucleotide IVS19+28 (IVS19+28T>C) resulting in no change in the predicted amino acid sequence; the first nucleotide of the initiating Met codon is numbered +1. |
| Miersch S, Espey MG, Chaube R, Akarca A, Tweten R, Ananvoranich S, Mutus B, Plasma membrane cholesterol content affects nitric oxide diffusion dynamics and signaling The Journal of biological chemistry: 2008 |
| PubMed ID: 18445594 |
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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 |
| Split Ratio |
1:3 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
10% fetal bovine serum Not inactivated |
| Substrate |
None specified |
| Subcultivation Method |
trypsin-EDTA |
| Supplement |
- |
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