GM03043
LCL from B-Lymphocyte
Description:
ADENOSINE DEAMINASE DEFICIENCY, PARTIAL
ADENOSINE DEAMINASE; ADA
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases |
| Class |
Disorders of Nucleotide and Nucleic Acid Metabolism |
| Alternate IDs |
GM17345 [ADENOSINE DEAMINASE DEFICIENCY, PARTIAL] |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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LCL from B-Lymphocyte
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Race
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Black/African American
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Ethnicity
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!KUNG
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Family Member
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1
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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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| messenger RNA |
Adrian et al (Mol Cell Biol 4:1712-1717 1984) performed S1 endonuclease cleavage of ADA cDNA-mRNA hybrids to show that the ADA mRNA from this culture yielded fragments that were distinctly different from ADA mRNA fragments from normal controls. The ADA cDNA utilized for these experiments represented the complete mRNA sequence with the possible exception of some of the 5 prime untranslated region. Hirschhorn et al (J Clin Invest 71:1887-1892 1983) reported that the ADA activity for this cell culture overlapped the normal range of activity but showed a markedly diminished heat stability. The enzyme showed a normal electrophoretic mobility and a normal isoelectric point of 4.9. |
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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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| adenosine deaminase |
According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.5.4.4; 10-12% activity. |
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| Gene |
ADA |
| Chromosomal Location |
20q13.11 |
| Allelic Variant 1 |
608958.0028; ADA DEFICIENCY, PARTIAL |
| Identified Mutation |
THR233ILE; In a healthy adult male of Afghanistani Kung descent, Hirschhorn et al. (1997) identified a homozygous 698C-T transition mutation of the ADA gene resulting in the amino acid change thr233ile. This mutation was found to have slightly greater enzymatic activity than the pathogenic mutation arg211cys (102700.0014). Immunologic studies done previously on the patient indicated an unstable ADA enzyme that was absent in red blood cells but present in sufficient amounts in other cell types to prevent accumulation of toxic metabolites and resulting immunodeficiency.
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| Gene |
ADA |
| Chromosomal Location |
20q13.11 |
| Allelic Variant 2 |
608958.0028; ADA DEFICIENCY, PARTIAL |
| Identified Mutation |
THR233ILE; In a healthy adult male of Afghanistani Kung descent, Hirschhorn et al. (1997) identified a homozygous 698C-T transition mutation of the ADA gene resulting in the amino acid change thr233ile. This mutation was found to have slightly greater enzymatic activity than the pathogenic mutation arg211cys (102700.0014). Immunologic studies done previously on the patient indicated an unstable ADA enzyme that was absent in red blood cells but present in sufficient amounts in other cell types to prevent accumulation of toxic metabolites and resulting immunodeficiency.
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| Remarks |
Phenotypically normal; !Kung South African; marked deficiency of red cell adenosine deaminase; 2-3% enzyme activity in RBCs, 10-12% enzyme activity in leukocytes, and 10-30% enzyme activity in cultured fibroblasts; ADA enzyme present in sufficeint amounts in cell types to prevent accumulation of toxic metabolites and resulting immunodeficiency; enzyme has ADA 1 electrophoretic mobility; normal humoral and cellular immunity; enzyme phenotypes: 6PGD=A, ADA=1, Neutral A-glucosidase C=2; contains unstable ADA protein and 3-4 times the normal level of normal ADA mRNA; donor subject is homozygous for a C>T transition at nucleotide 698 of the ADA gene [698C>T (alternately described as 793C>T)] resulting in a substitution of isoleucine for threonine at codon 233 [Thr233Ile(T233I)]; same donor as GM03029 fibroblast. |
| Kouprina N, Pavlicek A, Noskov VN, Solomon G, Otstot J, Isaacs W, Carpten JD, Trent JM, Schleutker J, Barrett JC, Jurka J, Larionov V, Dynamic structure of the SPANX gene cluster mapped to the prostate cancer susceptibility locus HPCX at Xq27 Genome research15:1477-86 2005 |
| PubMed ID: 16251457 |
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| Repping S, van Daalen SK, Brown LG, Korver CM, Lange J, Marszalek JD, Pyntikova T, van der Veen F, Skaletsky H, Page DC, Rozen S, High mutation rates have driven extensive structural polymorphism among human Y chromosomes Nature genetics38:463-7 2005 |
| PubMed ID: 16501575 |
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| Toomajian C, Kreitman M, Sequence variation and haplotype structure at the human HFE locus. Genetics161(4):1609-23 2002 |
| PubMed ID: 12196404 |
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| Tzall S, Ellenbogen A, Eng F, Hirschhorn R, Identification and characterization of nine RFLPs at the adenosine deaminase (ADA) locus. Am J Hum Genet44:864-75 1989 |
| PubMed ID: 2567118 |
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| Cann RL, Stoneking M, Wilson AC, Mitochondrial DNA and human evolution [see comments] Nature325:31-6 1987 |
| PubMed ID: 3025745 |
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| Hirschhorn R, Ellenbogen A, Genetic heterogeneity in adenosine deaminase (ADA) deficiency: five different mutations in five new patients with partial ADA deficiency. Am J Hum Genet38:13-25 1986 |
| PubMed ID: 3946419 |
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| Valerio D, Dekker BM, Duyvesteyn MG, van der Voorn L, Berkvens TM, van Ormondt H, van der Eb AJ, One adenosine deaminase allele in a patient with severe combined immunodeficiency contains a point mutation abolishing enzyme activity. EMBO J5:113-9 1986 |
| PubMed ID: 3007108 |
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| Adrian GS, Wiginton DA, Hutton JJ, Characterization of normal and mutant adenosine deaminase messenger RNAs by translation and hybridization to a cDNA probe. Hum Genet68:169-72 1984 |
| PubMed ID: 6548726 |
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| Adrian GS, Wiginton DA, Hutton JJ, Structure of adenosine deaminase mRNAs from normal and adenosine deaminase-deficient human cell lines. Mol Cell Biol4:1712-7 1984 |
| PubMed ID: 6208479 |
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| Adrian GS, Hutton JJ, Adenosine deaminase messenger RNAs in lymphoblast cell lines derived from leukemic patients and patients with hereditary adenosine deaminase deficiency. J Clin Invest71:1649-60 1983 |
| PubMed ID: 6134754 |
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| Hirschhorn R, Martiniuk F, Roegner-Maniscalco V, Ellenbogen A, Perignon JL, Jenkins T, Genetic heterogeneity in partial adenosine deaminase deficiency. J Clin Invest71:1887-92 1983 |
| PubMed ID: 6863546 |
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| Wiginton DA, Adrian GS, Friedman RL, Suttle DP, Hutton JJ, Cloning of cDNA sequences of human adenosine deaminase. Proc Natl Acad Sci U S A80:7481-5 1983 |
| PubMed ID: 6200875 |
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| Wiginton DA, Hutton JJ, Immunoreactive protein in adenosine deaminase deficient human lymphoblast cell lines. J Biol Chem257:3211-7 1982 |
| PubMed ID: 6977542 |
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| Hirschhorn R, Roegner V, Jenkins T, Seaman C, Piomelli S, Borkowsky W, Erythrocyte adenosine deaminase deficiency without immunodeficiency. Evidence for an unstable mutant enzyme. J Clin Invest64:1130-9 1979 |
| PubMed ID: 479373 |
| dbSNP |
dbSNP ID: 10594 |
| Gene Cards |
ADA |
| Gene Ontology |
GO:0004000 adenosine deaminase activity |
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GO:0009117 nucleotide metabolism |
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GO:0009168 purine ribonucleoside monophosphate biosynthesis |
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GO:0016787 hydrolase activity |
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GO:0019735 antimicrobial humoral response (sensu Vertebrata) |
| NCBI Gene |
Gene ID:100 |
| NCBI GTR |
102700 SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-NEGATIVE, DUE TO ADENOSINE DEAMINASE DEFICIENCY |
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608958 ADENOSINE DEAMINASE; ADA |
| OMIM |
102700 SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-NEGATIVE, DUE TO ADENOSINE DEAMINASE DEFICIENCY |
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608958 ADENOSINE DEAMINASE; ADA |
| Omim Description |
ADA-SCID, INCLUDED |
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ADENOSINE AMINOHYDROLASESEVERE COMBINED IMMUNODEFICIENCY DUE TO ADENOSINE DEAMINASE DEFICIENCY,INCLUDED |
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ADENOSINE DEAMINASE; ADA |
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SCID DUE TO ADA DEFICIENCY, INCLUDED |
| Split Ratio |
1:4 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Medium |
Roswell Park Memorial Institute Medium 1640 with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not Inactivated |
| Substrate |
None specified |
| Subcultivation Method |
dilution - add fresh medium |
| Supplement |
- |
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