GM20270

GM20270 Fibroblast from Skin, Unspecified

Description:

GAUCHER DISEASE, TYPE II
GLUCOSIDASE, ACID BETA; GBA

Affected:

Yes

Sex:

Female

Age:

4 MO (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Lysosomal Storage Diseases

Class

Disorders of Lipid Metabolism

Biopsy Source

Unspecified

Cell Type

Fibroblast

Tissue Type

Skin

Transformant

Untransformed

Sample Source

Fibroblast from Skin, Unspecified

Race

More than one race

Ethnicity

FILIPINO/AFRICAN

Family Member

Relation to Proband

proband

Confirmation

Molecular characterization before cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; donor subject is a compound heterozygote: one allele has a T>C transition at nucleotide 1448 in exon 10 of the GBA gene [1448T>C] resulting in a substitution of proline for leucine at codon 444 [Leu444Pro (L444P)] and a second allele has a splice site mutation in intron 2 of the GBA gene (IVS2+1G>A)

Characterizations

PDL at Freeze

6.54

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin confirmed by LINE assay

Gene

GBA

Chromosomal Location

1q21

Allelic Variant 1

606463.0001; GAUCHER DISEASE, NEURONOPATHIC

Identified Mutation

LEU483PRO (LEU444PRO), 1448T>C; The leu444-to-pro (L444P) substitution in exon 10 of the GBA gene has been reported as resulting from a 1448T-C transition (Zimran et al., 1989) and from a 6433T-C transition (Latham et al., 1990), depending upon the reference sequence cited. This mutation has alternatively been referred to as LEU483PRO (Saranjam et al., 2013).

Gene

GBA

Chromosomal Location

1q21

Allelic Variant 2

606463.0015; GAUCHER DISEASE

Identified Mutation

IVS2DS, G>A, +1; In a survey of 100 unrelated patients with Gaucher disease, 97 of whom were Jewish and 3 half-Jewish, Beutler et al. (1992) found that 2 of the alleles carried a previously unidentified nucleotide substitution at the first position in the splice donor site of intron 2, a change from G to A, causing skipping of exon 2. In addition to the splice site mutation in intron 2, mutations at nucleotides 1226 (230800.0003), 84 (230800.0014), 1448 (230800.0001), and 1297 (230800.0015) of the GBA cDNA were found repeatedly in unrelated Jewish subjects and accounted for 97.5% of all the mutations responsible for Gaucher disease in this population. The most common mutation, that at nucleotide 1226, present in homozygous state, was associated, on average, with the mildest disease and the latest age of onset. The mutation at nucleotide 84 and the IVS2 +1 mutation, which were associated with no enzyme, led to earlier onset and more severe disease. In a moderately affected 9-year-old Ashkenazi Jewish patient with type I Gaucher disease, He and Grabowski (1992) demonstrated a G-to-A transition at the first nucleotide of intron 2. The mutation destroyed the splice donor consensus site (U1 binding site) for mRNA processing and led to skipping of exon 2. This transition was found also at the corresponding exon/intron boundary of the highly homologous pseudogene. This splicing mutation accounted for about 3.4% of the Gaucher disease alleles in the Ashkenazi Jewish population. The occurrence of this pseudogene-type mutation in the structural gene indicates the role of the pseudogene and rearrangements of the structural gene in the pathogenesis of Gaucher disease.

Phenotypic Data

Remarks

Publications

Stone DL, Tayebi N, Orvisky E, Stubblefield B, Madike V, Sidransky E, Glucocerebrosidase gene mutations in patients with type 2 Gaucher disease. Hum Mutat15(2):181-8 2000

PubMed ID: 10649495