GM10874

GM10874 LCL from B-Lymphocyte

Description:

GAUCHER DISEASE, TYPE I
GLUCOSIDASE, ACID BETA; GBA

Affected:

Yes

Sex:

Male

Age:

11 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

Ethnicity

ASHKENAZI

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Ashkenazi; massive splenomegaly; mild hepatomegaly; about 8% of normal fibroblast acid B-glucosidase act; donor subject is a compound heterozygote: one allele carries a single-base mutation (adenosine to guanosine transition) in exon 9 at nucleotide 1226 (1226A>G) of the glucocerebrosidase gene (GBA) which results in the amino acid substitution of serine for asparagine [Asn370Ser (N370S)]; the second allele has a G>A transition at nucleotide 476 (476G>A) which results in the substitution of glutamine for arginine at codon 120 [Arg120Gln (R120Q)] [codons are numbered from the first codon of the mature protein; the cDNA is numbered from the first initiating AUG]

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

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

Gene

GBA

Chromosomal Location

1q21

Allelic Variant 1

606463.0003; GAUCHER DISEASE, TYPE I

Identified Mutation

ASN370SER; By nucleotide sequence analysis of a genomic clone from an Ashkenazi Jewish patient with type I, Tsuji et al. [Proc. Nat. Acad. Sci. 85: 2349-2352 (1988] found a single-base mutation (adenosine to guanosine transition) in exon 9 of the glucocerebrosidase gene. This change resulted in the amino acid substitution of serine for asparagine. Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity. This mutation [1226G (N370S)] accounts for approximately 70% of mutations in the Jewish population.

Gene

GBA

Chromosomal Location

1q21

Allelic Variant 2

606463.0004; GAUCHER DISEASE, TYPE I

Identified Mutation

ARG119GLN, 3060G>A; Graves et al. [DNA 7: 521 (1988)] identified a G-to-A transition leading to a change from arginine to glutamine at position 119. This was present in single dose in the index patient and his affected third cousin (i.e., they were genetic compounds). This was the second single base mutation found in Ashkenazi Jewish patients with Gaucher disease type I. This mutation is indicated as arg120gln by others, e.g., Latham et al. [Am. J. Hum. Genet. 47: 79 (1990)].

Phenotypic Data

Remarks

Publications

Yeeok Kang, Seong-Hyeuk Nam, Kyung Sun Park, Yoonjung Kim, Jong-Won Kim, Eunjung Lee, Jung Min Ko, Kyung-A Lee and Inho ParkEmail, DeviCNV: detection and visualization of exon-level copy number variants in targeted next-generation sequencing data BMC Bioinformatics19: 2018

PubMed ID: 30326846

Theophilus B, Latham T, Grabowski GA, Smith FI, Gaucher disease: molecular heterogeneity and phenotype-genotype correlations. Am J Hum Genet45:212-25 1989

PubMed ID: 2502917

Graves PN, Grabowski GA, Eisner R, Palese P, Smith FI, Gaucher disease type 1: cloning and characterization of a cDNA encoding acid beta-glucosidase from an Ashkenazi Jewish patient. DNA7:521-8 1988

PubMed ID: 3180993