GM04394

GM04394 Fibroblast

Description:

GAUCHER DISEASE, TYPE I
GLUCOSIDASE, ACID BETA; GBA

Affected:

Yes

Sex:

Male

Age:

1 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Lysosomal Storage Diseases
GeT-RM Samples

Class

Disorders of Lipid Metabolism

Cell Type

Fibroblast

Transformant

Untransformed

Race

Black/African American

Relation to Proband

proband

Confirmation

Molecular characterization after cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Hepatosplenomegaly; bone pain; no family history of disease; no neurologic abnormalities at age 2; 5% of control fibroblast glucocerebrosidase activity; donor subject is heterozygous for a T>C transition at nucleotide 1448 in exon 10 of the GBA gene [1448T>C] resulting in a substitution proline for leucine at codon 444 [Leu444Pro (L444P)] [codons are numbered from the first codon of the mature protein; the cDNA is numbered from the first initiating AUG].

Characterizations

PDL at Freeze

5.85

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase Isoenzyme Electrophoresis

MUTATION VERIFICATION

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 this patient to be heterozygous for a mutant allele. The mutant allele has a T to C transition at codon 444 that causes a substitution of proline for leucine and creates a new NciI restriction site. Two silent changes were found as well: ATT to ATC at amino acid 260 and GTG to GTC at residue 431.

MUTATION VERIFICATION

The L444P gene mutation in this sample has been verified by 6 laboratories. The S364T mutation has not been verified by multiple labs.

glucosylceramidase

According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.2.1.45; 5% activity.

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).

Phenotypic Data

Remarks

Publications

Kalman L, Wilson JA, Buller A, Dixon J, Edelmann L, Geller L, Highsmith WE, Holtegaard L, Kornreich R, Rohlfs EM, Payeur TL, Sellers T, Toji L, Muralidharan K, Development of genomic DNA reference materials for genetic testing of disorders common in people of ashkenazi jewish descent The Journal of molecular diagnostics : JMD11:530-6 2009

PubMed ID: 19815695

Sasagasako N, Kobayashi T, Yamaguchi Y, Shinnoh N, Goto I, Glucosylceramide and glucosylsphingosine metabolism in cultured fibroblasts deficient in acid beta-glucosidase activity. J Biochem (Tokyo)115:113-9 1994

PubMed ID: 8188616

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