Description:
GAUCHER DISEASE, TYPE I
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
GeT-RM Samples |
| 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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Ethnicity
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Eastern European Jewish
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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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 |
4.83 |
| Passage Frozen |
11 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
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| MUTATION VERIFICATION |
The N370S gene mutation in this sample has been verified by 6 laboratories and the V394L mutation has been verified by 4 laboratories. |
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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; 18% activity. |
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| 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. |
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| Gene |
GBA |
| Chromosomal Location |
1q21 |
| Allelic Variant 2 |
V394L; GAUCHER DISEASE, TYPE I |
| Identified Mutation |
VAL394LEU, 1297G>T |
| Remarks |
Hepatosplenomegaly since age 17; typical Gaucher's cells observed in bone marrow aspirant; 18% of control fibro 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 substitution of serine for asparagine at codon 370 [Asn370Ser (N370S)] and a second allele has a G>T transversion at nucleotide 1297 in exon 9 of the GBA gene [1297G>T] resulting in a substitution of leucine for valine at codon 394 [Val394Leu (V394L)];negative family history.
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| Scotto Rosato A, Krogsaeter EK, Jaslan D, Abrahamian C, Montefusco S, Soldati C, Spix B, Pizzo MT, Grieco G, Böck J, Wyatt A, Wünkhaus D, Passon M, Stieglitz M, Keller M, Hermey G, Markmann S, Gruber-Schoffnegger D, Cotman S, Johannes L, Crusius D, Boehm U, Wahl-Schott C, Biel M, Bracher F, De Leonibus E, Polishchuk E, Medina DL, Paquet D, Grimm C, TPC2 rescues lysosomal storage in mucolipidosis type IV, Niemann-Pick type C1, and Batten disease EMBO molecular medicine14:e15377 2022 |
| PubMed ID: 35929194 |
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| 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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| 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 |
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| 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 |
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| Pentchev PG, Comly ME, Kruth HS, Patel S, Proestel M, Weintroub H, The cholesterol storage disorder of the mutant BALB/c mouse. A primary genetic lesion closely linked to defective esterification of exogenously derived cholesterol and its relationship to human type C Niemann-Pick disease. J Biol Chem261:2772-7 1986 |
| PubMed ID: 3949747 |
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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 |
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| Choy FY, Gaucher disease: the effects of phosphatidylserine on glucocerebrosidase from normal and Gaucher fibroblasts. Hum Genet67:432-6 1984 |
| PubMed ID: 6436168 |
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| Silverstein E, Friedland J, Angiotensin converting enzyme in cultured fibroblasts in Gaucher and Niemann-Pick diseases. Proc Soc Exp Biol Med170:251-3 1982 |
| PubMed ID: 6283559 |
| dbSNP |
dbSNP ID: 10426 |
| 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 |
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Gene ID:2630 |
| NCBI GTR |
230800 GAUCHER DISEASE, TYPE I; GD1 |
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606463 GLUCOSIDASE, BETA, ACID; GBA |
| OMIM |
230800 GAUCHER DISEASE, TYPE I; GD1 |
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606463 GLUCOSIDASE, BETA, ACID; GBA |
| Omim Description |
ACID BETA-GLUCOSIDASE DEFICIENCY |
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GAUCHER DISEASE, NONCEREBRAL JUVENILE |
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GAUCHER DISEASE, TYPE I |
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GBA DEFICIENCYGLUCOSIDASE, ACID BETA, INCLUDED; GBA, INCLUDED |
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GD I |
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GLUCOCEREBROSIDASE DEFICIENCY |
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GLUCOCEREBROSIDASE PSEUDOGENE, INCLUDED; GBAP, INCLUDED |
| Passage Frozen |
11 |
| Split Ratio |
1:2 |
| 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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