NA00852

NA00852 DNA from Fibroblast

Description:

GAUCHER DISEASE, TYPE I
GLUCOSIDASE, ACID BETA; GBA

Affected:

Yes

Sex:

Male

Age:

20 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Lysosomal Storage Diseases
GeT-RM Samples

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

Family Member

Relation to Proband

proband

Confirmation

Molecular characterization after cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

6% of control fibroblast glucocerebrosidase activity; donor subject is a compound heterozygote: one allele has an A>G transition at nucleotide 1226 in exon 9 of the GBA gene [1226A>G] resulting in a subtitution of serine for asparagine at codon 370 [Asn370Ser (N370S)] and a second allele has an insertion of a second guanine at cDNA nucleotide 84 [84_85insG, 84GG] (codons are numbered from the first codon of the mature protein; the cDNA is numbered from the first initiating AUG).

Characterizations

PDL at Freeze

4.7

Passage Frozen

GENE MAPPING & DOSAGE STUDIES - Y CHROMOSOME

PCR analysis of DNA from this cell culture gave a positive result with a primer for Yq11, DYS227.

IDENTIFICATION OF SPECIES OF ORIGIN

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

MUTATION VERIFICATION

The gene mutation(s) in this sample have been verified by 6 laboratories.

glucosylceramidase

According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.2.1.45; 6% activity.

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

606463.0014; GAUCHER DISEASE, TYPE I

Identified Mutation

1-BP INS, 84G; Beutler et al. [Proc. Nat. Acad. Sci. 88: 10544-10547 (1991)] found a second common Jewish Gaucher disease mutation in addition to the A-to-G mutation of nucleotide 1226, which accounts for about 75% of mutant alleles in Ashkenazi Jews (606463.0003). The new mutation consisted of insertion of a second guanine at cDNA nucleotide 84 and was referred to as the 84GG mutation. The 84GG and A1226G mutations, along with the less-common mutation at nucleotide 1448 (606463.0001), account for 95% of all Gaucher disease-producing alleles in Ashkenazi Jews.

Phenotypic Data

Remarks

Publications

Basgalupp SP, Siebert M, Ferreira C, Behringer S, Spiekerkoetter U, Hannibal L, Schwartz IVD, Assessment of cellular cobalamin metabolism in Gaucher disease BMC medical genetics21:12 2019

PubMed ID: 31931749

Chen Y1,2, Jian J1, Hettinghouse A1, Zhao X3, Setchell KDR3, Sun Y3, Liu CJ4,5, Progranulin associates with hexosaminidase A and ameliorates GM2 ganglioside accumulation and lysosomal storage in Tay-Sachs disease J Mol Med96:1359-1373 2018

PubMed ID: 30341570

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 Bioinformatics19:1359-1373 2018

PubMed ID: 30326846

Mazzulli JR, Xu YH, Sun Y, Knight AL, McLean PJ, Caldwell GA, Sidransky E, Grabowski GA, Krainc D, Gaucher disease glucocerebrosidase and a-synuclein form a bidirectional pathogenic loop in synucleinopathies Cell146:37-52 2010

PubMed ID: 21700325

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

Park IH, Arora N, Huo H, Maherali N, Ahfeldt T, Shimamura A, Lensch MW, Cowan C, Hochedlinger K, Daley GQ, Disease-Specific Induced Pluripotent Stem Cells Cell134(5):877-86 2008

PubMed ID: 18691744

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

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

Turner BM, Hirschhorn K, Properties of beta-glucosidase in cultured skin fibroblasts from controls and patients with Gaucher disease. Am J Hum Genet30:346-58 1978

PubMed ID: 102189

Neufeld EF, Liebaers I, Epstein CJ, Yatziv S, Milunsky A, Migeon BR, The Hunter syndrome in females: is there an autosomal recessive form of iduronate sulfatase deficiency? Am J Hum Genet29:455-61 1977

PubMed ID: 409284