GM23154

GM23154 LCL from B-Lymphocyte

Description:

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

Affected:

Yes

Sex:

Male

Age:

12 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Lysosomal Storage Diseases

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Family History

Relation to Proband

proband

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; weight loss; slow swallowing; frequent partial seizures; disturbed sleep patterns; suspected hypnopompic hallucinations; hypersomnolent; limb weakness; difficulty with coordination; often sad, restless, irritable or angry; progressive ataxia and dystonia; ataxic dysarthria; speech has become less intelligible; vertical and early horizontal supranuclear gaze palsy; donor subject is a compound heterozygote: one allele has a G>A transition at nucleotide 1211 in exon 8 of the NPC1 gene (c.1211G>A) resulting in the substitution of glutamine for arginine at codon 404 [Arg404Gln (R404Q)] and the second allele has a C>G transversion at nucleotide 3019 in exon 20 (c.3019C>G) resulting in the substitution of alanine for proline at codon 1007 [Pro1007Ala (P1007A)]; donor subject is also heterozygous for an expanded GAA tracked in the FRDA gene (FXN): the expanded allele has 196 GAA repeats

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by LINE assay

Gene

FXN

Chromosomal Location

9q13-q21.1

Allelic Variant 1

606829.0001; FRIEDREICH ATAXIA

Identified Mutation

(GAA)n EXPANSION; GAA triplet repeat expansions between 200 and 900 copies in the first intron of the frataxin gene occurred in 71 out of 74 FRDA patients studied by Campuzano et al. [Science 271: 1423-1427 (1996)]. In unaffected individuals the triplet expansion numbered between 7 and 20 units.

Gene

NPC1

Chromosomal Location

18q11-q12

Allelic Variant 1

R404Q; NIEMANN-PICK DISEASE, TYPE C1

Identified Mutation

ARG404GLN

Gene

NPC1

Chromosomal Location

18q11-q12

Allelic Variant 2

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.