GM02294
LCL from B-Lymphocyte
Description:
SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-NEGATIVE, DUE TO ADENOSINE DEAMINASE DEFICIENCY
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 |
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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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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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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase Isoenzyme Electrophoresis |
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| adenosine deaminase |
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 was 10-15% of normal and had a diminished heat stability. The enzyme showed a normal electrophoretic mobility but had a more basic isoelectric point than normal (5.0 vs 4.9). EC Number: 3.5.4.4; 10-15% activity. |
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| Gene |
ADA |
| Chromosomal Location |
20q13.11 |
| Allelic Variant 1 |
608958.0015; ADA DEFICIENCY, PARTIAL |
| Identified Mutation |
ALA215THR; In cell line GM02294, Hirschhorn et al. [Proc Natl Acad Sci U S A 87: 6171 (1990)] found homozygosity for a G-to-A transition of nucleotide 643 in exon 7 resulting in a change of alanine215-to-threonine. |
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| Gene |
ADA |
| Chromosomal Location |
20q13.11 |
| Allelic Variant 2 |
608958.0015; ADA DEFICIENCY, PARTIAL |
| Identified Mutation |
ALA215THR; In cell line GM02294, Hirschhorn et al. [Proc Natl Acad Sci U S A 87: 6171 (1990)] found homozygosity for a G-to-A transition of nucleotide 643 in exon 7 resulting in a change of alanine215-to-threonine. |
| Remarks |
Clinically affected; born at 8 months gestation due to placenta previa; bilateral polydactyly and hypospadias noted at birth; IVP demonstrated obstruction at the left ureteropelvic junction and possible vesicoureteral reflux with minimal dilation of the calyces; in first week of life chest x-ray suggested right lower lobe infiltrate; ADA deficiency of red blood cells was identified through neonatal screening for inherited disordes; normal thymic shadow; height and weight progressed from 3rd to 25th percentile at 20 months of age; normal development; transient hypogammaglobulinemia; normal serum levels of IgG, IgM, IgA, & IgE at 10-12 months of age; eosiniphilia but isoagglutinins are present; deficient RBC ADA activity; partial ADA deficiency in fibroblasts & lymphoblasts; enzyme phenotypes: 6PGD=A, G6PD=B, ADA=1, Neutral A-glucosidase C=2; donor subject is homozygous for a G>A transition at nucleotide 643 in exon 7 of the ADA gene [643G>A] resulting in a substitution of threonine for alanine at codon 215 [Ala215Thr(A215T)]; same donor as GM01997 fibroblast. |
| 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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| 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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| Danton MJ, Coleman MS, Isolation of mutant adenosine deaminase by coformycin affinity chromatography. Anal Biochem159:233-9 1986 |
| PubMed ID: 3492941 |
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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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| Erikson J, ar-Rushdi A, Drwinga HL, Nowell PC, Croce CM, Transcriptional activation of the translocated c-myc oncogene in burkitt lymphoma. Proc Natl Acad Sci U S A80:820-824 1983 |
| PubMed ID: 6402776 |
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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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| Nishikura K, ar-Rushdi A, Erikson J, Watt R, Rovera G, Croce CM, Differential expression of the normal and of the translocated human c- myc oncogenes in B cells. Proc Natl Acad Sci U S A80:4822-6 1983 |
| PubMed ID: 6308654 |
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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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| Daddona PE, Kelley WN, Characteristics of an aminohydrolase distinct from adenosine deaminase in cultured human lymphoblasts. Biochim Biophys Acta658:280-90 1981 |
| PubMed ID: 6972784 |
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| Borkowsky W, Gershon AA, Shenkman L, Hirschhorn R, Adenosine deaminase deficiency without immunodeficiency: clinical and metabolic studies. Pediatr Res14:885-9 1980 |
| PubMed ID: 6251420 |
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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: 16791 |
| 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 |
1:3 |
| 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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