GM03124

GM03124 LCL from B-Lymphocyte

Description:

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

Affected:

Yes

Sex:

Female

Age:

9 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Lysosomal Storage Diseases

Class

Disorders of Lipid Metabolism

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Family Member

Relation to Proband

proband

Confirmation

Biochemical characterization - other

Species

Homo sapiens

Common Name

Human

Remarks

38% of normal sphingomyelinase activity, normal B-galactosidase activity, and impaired cholesterol esterification in fibroblasts; the donor subject is a compound heterozygote; one allele carries a pathogenic splice site mutation c.1947+5G>C (rs770321568, g.41940G>C), as well as a missense mutation c.709C>T [p.Pro237Ser (P237S); rs80358251] in exon 6 of the NPC1 gene; the second allele carries a pathogenic missense mutation c.3182T>C in exon 21 [p.Ile1061Thr (I1061T)] in a transmembrane domain; same subject as GM03123 (fibroblast) and GM25864 (stem cell).

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase Isoenzyme Electrophoresis

sphingomyelin phosphodiesterase

According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.1.4.12; 38% activity.

Gene

NPC1

Chromosomal Location

18q11-q12

Allelic Variant 1

P237S; NIEMANN-PICK DISEASE, TYPE C1

Identified Mutation

PRO237SER

Gene

NPC1

Chromosomal Location

18q11-q12

Allelic Variant 1

; NIEMANN-PICK DISEASE, TYPE C1

Identified Mutation

c.1947+5G>C

Gene

NPC1

Chromosomal Location

18q11-q12

Allelic Variant 2

607623.0010; NIEMANN-PICK DISEASE, TYPE C1

Identified Mutation

ILE1061THR; In an initial study of 25 patients with type C1 Niemann-Pick disease, Millat et al. [Am. J. Hum. Genet. 65: 1321-1329 (1999)] identified a T-to-C transition at nucleotide 3182 of the NPC1 gene that led to an ile1061-to-thr substitution (I1061T) in 3 patients. The mutation, located in exon 21, affected a putative transmembrane domain of the protein. The mutation was particularly frequent in patients with NPC from western Europe, especially France and the U.K. and in Hispanic patients whose roots were in the Upper Rio Grande valley of the U.S. Millat et al. [Am. J. Hum. Genet. 65: 1321-1329 (1999)] concluded that the I1061T mutation originated in Europe and that the high frequency in northern Rio Grande Hispanics resulted from a founder effect.

Phenotypic Data

Remarks

Publications

Wheeler S, Haberkant P, Bhardwaj M, Tongue P, Ferraz MJ, Halter D, Sprong H, Schmid R, Aerts JMFG, Sullo N, Sillence DJ, Cytosolic glucosylceramide regulates endolysosomal function in Niemann-Pick type C disease Neurobiology of disease127:242-252 2018

PubMed ID: 30872158

Ramirez-Montealegre D, Pearce DA, Defective lysosomal arginine transport in juvenile Batten disease Human molecular genetics14:3759-73 2005

PubMed ID: 16251196

Yamamoto T, Nanba E, Ninomiya H, Higaki K, Taniguchi M, Zhang H, Akaboshi S, Watanabe Y, Takeshima T, Inui K, Okada S, Tanaka A, Sakuragawa N, Millat G, Vanier MT, Morris JA, Pentchev PG, Ohno K, NPC1 gene mutations in Japanese patients with Niemann-Pick disease type C. Hum Genet105:10-6 1999

PubMed ID: 10480349

Levade T, Salvayre R, Lenoir G, Douste-Blazy L, Sphingomyelinase and nonspecific phosphodiesterase activities in Epstein-Barr virus-transformed lymphoid cell lines from Niemann-Pick disease A, B and C. Biochim Biophys Acta793:321-4 1984

PubMed ID: 6324871