GM18387

GM18387 Fibroblast

Description:

NIEMANN-PICK DISEASE, TYPE C1; NPC1
NPC1 GENE; NPC1

Affected:

Yes

Sex:

Female

Age:

No Data

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Lysosomal Storage Diseases

Class

Disorders of Lipid Metabolism

Cell Type

Fibroblast

Transformant

Untransformed

Race

White

Relation to Proband

proband

Confirmation

Molecular characterization before cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; diagnosed at 33 yr; deceased one week before 40th birthday; other family members with NPC; neonatal jaundice; yellow sclera for three days; MRI showed iron deposits, mild sucal widening, and bilateral frontal hyperperfusion; ataxia; vertical gaze palsy; dysarthria; dysphagia; organic affective disorder; sleep walking; moderate movement difficulty; no verbal communication; constant difficulty swallowing; fibroblasts showed 44 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 type 1 (see Park et al., 2003); the donor subject is a compound heterozygote at the NPC1 gene locus: allele 1 carries a substitution (A>T) at nucleotide 2621 (c.2621A>T) in exon 18, resulting in a missense mutation at codon 874 [D874V (ASP874VAL)]; allele 2 carries a substitution (C>G) at nucleotide 2670 (c.2670C>G) in exon 18, resulting in a nonsense mutation at codon 890 [Y890X (TYR890TER)]; the subject also carries the following polymorphisms: (T>C) at nucleotide 387 (387T>C) resulting in a silent mutation (Y>Y) at codon 129 [Y129Y, (TYR129TYR)]; (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; the first nucleotide of the initiating MET codon is numbered +1. This fibroblast is a characteristically poor grower and will only be shipped frozen; requires particular care during growth; the recommended seeding density is 15,000 to 20,000 cells per cm2.

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase,Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis

Gene

NPC1

Chromosomal Location

18q11-q12

Allelic Variant 1

D874V; NIEMANN-PICK DISEASE, TYPE C1

Identified Mutation

ASP874VAL

Gene