NA17912
DNA from Fibroblast
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 |
| Quantity |
10 µg |
| Quantitation Method |
Please see our FAQ |
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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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Sample Source
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DNA from Fibroblast
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Race
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White
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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 |
607623.0012; NIEMANN-PICK DISEASE, TYPE C1 |
| Identified Mutation |
PRO1007ALA; In 3 families with variant Niemann-Pick disease type C1 (257220), Millat et al. (Am. J. Hum. Genet. 68: 1373-1385, 2001) found compound heterozygosity for the 2 most common alleles of the NPC1 gene, I1061T (607623.0010) and P1007A. Compound heterozygosity of these 2 alleles resulted in the juvenile onset of symptoms and a significantly slower progression of the disease than in homozygous I1061T patients. |
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| Gene |
NPC1 |
| Chromosomal Location |
18q11-q12 |
| Allelic Variant 2 |
607623.0002; NIEMANN-PICK DISEASE, TYPE C1 |
| Identified Mutation |
THR1036MET; In a patient with NPC disease, Carstea et al. (1997) observed homozygosity for a 3107C-T transition of the NPC1 gene that resulted in a thr1036-to-met amino acid substitution. The same mutation was found as one allele in a compound heterozygote. This patient was apparently unrelated to the first.
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| Remarks |
Clinically affected; diagnosed at age 11 yr; deceased at age 19 yr; neonatal jaundice; clumsy; learning difficulties; ataxia; dysarthria; dysphagia; gastrostomy; seizures; wheelchair bound; severe movement difficulties; absent communication; tube fed; fibroblasts showed 633 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 "other"/type 1 in a filipin staining assay (see Park et al., 2003); a complementation test showed that the cells were of the "other"/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 (C>G) at nucleotide 3019 (c.3019C>G) in exon 20, resulting in a missense mutation at codon 1007 [ P1007A (PRO1007ALA)]; allele 2 carries a substitution (C>T) at nucleotide 3107 (c.3107C>T) in exon 21, resulting in a missense mutation at codon 1036 [T1036M (THR1036MET)]; the subject also carries the following polymporphisms: 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)]; and 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. |
| Schultz ML, Fawaz MV, Azaria RD, Hollon TC, Liu EA, Kunkel TJ, Halseth TA, Krus KL, Ming R, Morin EE, McLoughlin HS, Bushart DD, Paulson HL, Shakkottai VG, Orringer DA, Schwendeman AS, Lieberman AP, Synthetic high-density lipoprotein nanoparticles for the treatment of Niemann-Pick diseases BMC medicine17:200 2019 |
| PubMed ID: 31711490 |
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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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| 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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| 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 |
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