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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| Passage Frozen |
16 |
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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 |
; NIEMANN-PICK DISEASE, TYPE C1 |
| Identified Mutation |
451_452delAG |
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| Gene |
NPC1 |
| Chromosomal Location |
18q11-q12 |
| Allelic Variant 2 |
Y825C; NIEMANN-PICK DISEASE, TYPE C1 |
| Identified Mutation |
TYR825CYS |
| Remarks |
Clinically affected; diagnosed at age 21 yr; deceased at 32 yr; family history of NPC; clumsy; learning difficulties; ataxia; vertical gaze palsy; dysarthria; dysphagia; psychiatric disorder; absence of communication; difficulty with movement; constant difficulty swallowing; fibroblasts showed 10 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 2 bp deletion mutation (delAG) at nucleotide 451 (c.451_452delAG; 451delAG) in exon 4; allele 2 carries a substitution of A>G at nucleotide 2474 (c.2474A>G) in exon 16, resulting in a missense mutation at codon 825 [Y825C (TYR825CYS)]; the subject also carries the following polymorphism: A>G at nucleotide 644 (c.644A>G) resulting in the substitution of arginine for histidine (H>R) at codon 215 [H215R (HIS215ARG)]; the first nucleotide of the initiating Met codon is numbered +1. |
| Pepponi R, De Simone R, De Nuccio C, Visentin S, Matteucci A, Bernardo A, Popoli P, Ferrante A, Repurposing Dipyridamole in Niemann Pick Type C Disease: A Proof of Concept Study International journal of molecular sciences23: 2022 |
| PubMed ID: 35408815 |
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| Schultz ML, Krus KL, Kaushik S, Dang D, Chopra R, Qi L, Shakkottai VG, Cuervo AM, Lieberman AP, Coordinate regulation of mutant NPC1 degradation by selective ER autophagy and MARCH6-dependent ERAD Nature communications9:3671 2017 |
| PubMed ID: 30202070 |
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| Visentin S, De Nuccio C, Bernardo A, Pepponi R, Ferrante A, Minghetti L, Popoli P, The stimulation of adenosine A2A receptors ameliorates the pathological phenotype of fibroblasts from Niemann-Pick type C patients The Journal of neuroscience : the official journal of the Society for Neuroscience33:15388-93 2013 |
| PubMed ID: 24068806 |
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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 |
16 |
| Split Ratio |
1:3 |
| 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 |
| Substrate |
None specified |
| Subcultivation Method |
trypsin-EDTA |
| Supplement |
- |
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