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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Ethnicity
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CANADIAN/ITALIAN
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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 |
5.6 |
| Passage Frozen |
9 |
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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 |
E612D; NIEMANN-PICK DISEASE, TYPE C1 |
| Identified Mutation |
GLU612ASP |
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| Gene |
NPC1 |
| Chromosomal Location |
18q11-q12 |
| Allelic Variant 2 |
F542fsX; NIEMANN-PICK DISEASE, TYPE C1 |
| Identified Mutation |
c.1628delC |
| Remarks |
Clinically affected; abdominal distension; diagnosed at 14 months; alive at 7 year; colic at 5 months; mild neonatal jaundice; normal development; hepatosplenomegaly; liver biopsy shows storage in Kupffer cells consistent with NP; clumsy; learning difficulties; ataxia; vertical gaze palsy; dysarthria; cataplexy; dysphagia; gastrostomy; asthma; seizures; sleeping problems; wheelchair bound; absent communication; fibroblasts showed no detectable activity in a cholesterol esterification assay; donor subject is a compound heterozygote at the NPC1 gene locus: allele 1 carries a substitution (A>C) at nucleotide 1836 (c.1836A>C) in exon 10, resulting in a missense mutation at codon 612 [Glu612Asp (E612D)]; allele 2 carries a one base pair deletion at nucleotide 1628 (c.1628delC) in exon 17, results in a frameshift mutation at codon 542 (F542fsX); the subject also carries the following polymorphisms: (A>G) at nucleotide 644 (644A>G) resulting in a missense mutation (H>R) at codon 215 [H215R (His215Arg)]; A>G at nucleotide 2572 (2572A>G) in exon 17 which results in a missense mutation (I>V) at codon 858 [I858V (Ile858Val)]; (C>G) at nucleotide 1926 (1926C>G) in exon 12 resulting in a missense mutation (I>M) at codon 642 [I642M (Ile642Met)]; IVS12+8(G)9-14; (C>T) at nucleotide 2793 (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. |
| Liedtke M, Völkner C, Hermann A, Frech MJ, Impact of Organelle Transport Deficits on Mitophagy and Autophagy in Niemann-Pick Disease Type C Cells11: 2022 |
| PubMed ID: 35159316 |
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| Králová J, Popr M, Valecka J, Bartunek P, Sterolight as imaging tool to study sterol uptake, trafficking and efflux in living cells Scientific reports12:6264 2021 |
| PubMed ID: 35428843 |
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| Völkner C, Pantoom S, Liedtke M, Lukas J, Hermann A, Frech MJ, Assessment of FDA-Approved Drugs as a Therapeutic Approach for Niemann-Pick Disease Type C1 Using Patient-Specific iPSC-Based Model Systems Cells11:6264 2021 |
| PubMed ID: 35159129 |
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| Králová J, Jurášek M, Mikšátková L, Marešová A, Fähnrich J, Cihlárová P, Drašar P, Bartunek P, Král V, Influence of fluorophore and linker length on the localization and trafficking of fluorescent sterol probes Scientific reports10:22053 2020 |
| PubMed ID: 33328481 |
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| Wang C, Scott SM, Subramanian K, Loguercio S, Zhao P, Hutt DM, Farhat NY, Porter FD, Balch WE, Quantitating the epigenetic transformation contributing to cholesterol homeostasis using Gaussian process Nature communications10:5052 2018 |
| PubMed ID: 31699992 |
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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 |
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| Appelqvist H, Sandin L, Björnström K, Saftig P, Garner B, Ollinger K, Kågedal K, Sensitivity to lysosome-dependent cell death is directly regulated by lysosomal cholesterol content PloS one7:e50262 2012 |
| PubMed ID: 23166840 |
| Passage Frozen |
9 |
| 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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