Description:
GAUCHER DISEASE, TYPE II
GLUCOSIDASE, ACID BETA; GBA
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Lysosomal Storage Diseases |
| Class |
Disorders of Lipid Metabolism |
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Cell Type
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Fibroblast
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Transformant
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Untransformed
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Race
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White
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Relation to Proband
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proband
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Confirmation
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Molecular characterization after cell line submission to CCR
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| PDL at Freeze |
6.05 |
| Passage Frozen |
4 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase Isoenzyme Electrophoresis |
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| 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). |
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| glucosylceramidase |
According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.2.1.45; 24% activity. |
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| 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). |
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| 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). |
| 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] |
| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
| dbSNP |
dbSNP ID: 20756 |
| Gene Cards |
GBA |
| Gene Ontology |
GO:0004348 glucosylceramidase activity |
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GO:0005764 lysosome |
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GO:0005975 carbohydrate metabolism |
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GO:0006665 sphingolipid metabolism |
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GO:0007040 lysosome organization and biogenesis |
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GO:0016020 membrane |
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GO:0016798 hydrolase activity, acting on glycosyl bonds |
| NCBI Gene |
Gene ID:2629 |
| NCBI GTR |
230900 GAUCHER DISEASE, TYPE II; GD2 |
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606463 GLUCOSIDASE, BETA, ACID; GBA |
| OMIM |
230900 GAUCHER DISEASE, TYPE II; GD2 |
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606463 GLUCOSIDASE, BETA, ACID; GBA |
| Omim Description |
GAUCHER DISEASE, ACUTE NEURONOPATHIC TYPE |
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GAUCHER DISEASE, INFANTILE CEREBRAL |
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GAUCHER DISEASE, TYPE II |
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GD II |
| Passage Frozen |
4 |
| Split Ratio |
1:4 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
AMBIENT |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Supplement |
- |
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