NA02627

NA02627 DNA from Fibroblast

Description:

GAUCHER DISEASE, TYPE II
GLUCOSIDASE, ACID BETA; GBA

Affected:

Yes

Sex:

Female

Age:

3 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Lysosomal Storage Diseases

Class

Disorders of Lipid Metabolism

Quantity

10 µg

Quantitation Method

Please see our FAQ

Cell Type

Fibroblast

Transformant

Untransformed

Sample Source

DNA from Fibroblast

Race

White

Relation to Proband

proband

Confirmation

Molecular characterization after cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Atypical; subacute neuropathic Gaucher; myoclonus; seizures; expired at age 3 due to pneumonia; 24% of control fibroblast glucocerebrosidase activity; donor subject is a compound heterozygote: one allele has a G>A transition at nucleotide 1090 in exon 8 of the GBA gene (1090G>A) resulting in a substitution of arginine for glycine at codon 325 [Gly325Arg(G325R)]; the second allele has a T>G transition at nucleotide 1141 in exon 8 (1141T>G) resulting in the substitution of glycine for cysteine at codon 342 [Cys342Gly(C342G)] [codons are numbered from the first codon of the mature protein; the cDNA is numbered from the first initiating AUG]

Characterizations

PDL at Freeze

6.05

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase Isoenzyme Electrophoresis

MUTATION VERIFICATION

Bergman and Grabowski (Am J Hum Genet 44:741-750 1989) analyzed the major processing steps in the maturation of the lysosomal hydrolase acid B-glucosidase in this type II Gaucher disease fibroblast culture. In normal fibroblasts remodeling of N-linked oligosaccharides resulted in the temporal appearance of three molecular-weight forms of acid B-glucosidase. An initial 64-KDa form containing high mannose-type oligosaccharide side chains was processed quantitatively within 24h to a sialylated 69-KDa form. During the subsequent 96h some of the 69-KDa form is processed to 59-KDa. GM02627 fibroblasts were able to process some of the 64-KDa form of the enzyme to the 69-KDa form. In addition some of the 64-KDa enzyme was still present after 24h. The 69-KDa form of the enzyme disappeared more rapidly than in normal fibroblasts. No conversion to the normally present 59-KDa form was observed. Wigderson et al (Am J Hum Genet 44:365-377 1989) characterized the human glucocerebrosidase gene from Gaucher disease patients. The results obtained with DNA from this cell culture showed that this patient lacked both the C to G transversion at codon 415 which creates a new HhaI restriction site and the T to C transition at codon 444 which creates a new NciI restriction site which had been found for other Gaucher disease patients. These results were confirmed and extended by Theophilus et al (Am J Hum Genet 45:212-225 1989). These authors reported that this type II patient lacked all four currently known acidB-glucosidase gene mutations: the T to C transition in exon 10 (Leu 444 to Pro 444) the C to G transversion in exon 9 (Pro 415 to Arg 415) the A to G transition in exon 9 (Asp 370 to Ser 370) and the G to A transition in exon 5 (Arg 120 to Gln 120).

glucosylceramidase

According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.2.1.45; 24% activity.

Gene

GBA

Chromosomal Location

1q21

Allelic Variant 1

606463.0030; GAUCHER DISEASE, TYPE II

Identified Mutation

GLY325ARG; In a type II Gaucher disease patient, Eyal et al. [Gene 96: 277 (1990)] identified a 5306G-A transition of the GBA gene leading to a change from glycine to arginine at position 325. The patient was a compound heterozygote for a cys342gly substitution (230800.0031).

Gene

GBA

Chromosomal Location

1q21

Allelic Variant 2

606463.0031; GAUCHER DISEASE, TYPE II

Identified Mutation

CYS342GLY; In a type II Gaucher disease patient, Eyal et al. [Gene 96:277 (1990)] identified a 5357T-G transversion of the GBA gene leading to a change from cysteine to glycine at position 342. The patient was a compound heterozygote for a gly325arg substitution (230800.0030).

Phenotypic Data

Remarks

Publications

Fog CK, Zago P, Malini E, Solanko LM, Peruzzo P, Bornaes C, Magnoni R, Mehmedbasic A, Petersen NHT, Bembi B, Aerts JFMG, Dardis A, Kirkegaard T, The heat shock protein amplifier arimoclomol improves refolding, maturation and lysosomal activity of glucocerebrosidase EBioMedicine38:142-153 2018

PubMed ID: 30497978

Bergmann JE, Grabowski GA, Posttranslational processing of human lysosomal acid beta-glucosidase: a continuum of defects in Gaucher disease type 1 and type 2 fibroblasts. Am J Hum Genet44:741-50 1989

PubMed ID: 2495719

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

Wigderson M, Firon N, Horowitz Z, Wilder S, Frishberg Y, Reiner O, Horowitz M, Characterization of mutations in Gaucher patients by cDNA cloning. Am J Hum Genet44:365-77 1989

PubMed ID: 2464926

Reiner O, Wilder S, Givol D, Horowitz M, Efficient in vitro and in vivo expression of human glucocerebrosidase cDNA. DNA6:101-8 1987

PubMed ID: 2438102

Beutler E, Kuhl W, Sorge J, Cross-reacting material in Gaucher disease fibroblasts. Proc Natl Acad Sci U S A81:6506-10 1984

PubMed ID: 6593712