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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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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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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Biochemical 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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| 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; <1.5% activity. |
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| Gene |
ADA |
| Chromosomal Location |
20q13.11 |
| Allelic Variant 1 |
608958.0005; SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-NEGATIVE, DUE TO ADENOSINE DEAMINASE DEFICIENCY |
| Identified Mutation |
LEU304ARG; In a patient with SCID due to ADA deficiency (102700) originally reported by Hirschhorn et al. (1975), Valerio et al. (1986) identified compound heterozygosity for 2 mutations in the ADA gene: one was a T-to-G transversion in exon 10, resulting in a leu304-to-arg (L304R) substitution. Functional expression studies showed that the L304R substitution resulted in ADA enzyme inactivation. |
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| Gene |
ADA |
| Chromosomal Location |
20q13.11 |
| Allelic Variant 2 |
608958.0018; SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-NEGATIVE, DUE TO ADENOSINE DEAMINASE DEFICIENCY |
| Identified Mutation |
ARG156CYS; In 2 patients with SCID who were unusual for reportedly responding to the limited form of enzyme therapy provided by repeated partial exchange transfusions {Polmar et al. [N Engl J Med 295: 1337 (1976); Dyminski et al. [Clin Immunol Immunopathol 14: 307 (1979)]}, Hirschhorn [Hum Mutat 1: 166 (1992)] found two new missense mutations, arg156-to-cys and ser291-to-leu (102700.0019). The first of these was found in cell line GM02471 and represented a CGC-to-TGC transition at codon 156. |
| Remarks |
Clinically affected; physical exam at birth was normal; subject was placed in protective isolation after birth and had good weight gain and no infections during the first 6 weeks; no thymic shadow seen on chest x-ray; perianal abscesses were intermittently present between one and ten months of age; normal development; normal kidneys but possible obstruction of left ureter; T cells were 44% and 46% at 3 and 9 days of age, respectively and B cells were 43% and 19%, respectively; leukopenia; immunoglobulin levels at 20 days of age were normal; deficient RBC & fibroblast ADA activity; residual ADA activity could be detected in mononuclear-cell/platelet preparations; less than 1.5% of ADA activity was seen in amniotic fluid cells; enzyme phenotypes: G6PD=B; 6PGD=A; peptidases A, C, & D=1; & PGM 1 & 3=1; donor subject is a compound heterozygote: one allele has a T>G transversion at nucleotide 911 in exon 10 of the ADA gene [911T>G] resulting in a substitution of arginine for leucine at codon 304 [Leu304Arg (L304R)] and a second allele has a C>T transition at nucleotide 466 of the ADA gene [466C>T] resulting in a substitution of cysteine for arginine at codon 156 [Arg156Cys (R156C)]; affected sister died at 9 months of age; mother is GM02433; same donor as GM02471 lymphocyte. |
| Daddona PE, Frohman MA, Kelley WN, Human adenosine deaminase and its binding protein in normal and adenosine deaminase-deficient fibroblast cell strains. J Biol Chem255:5681-7 1980 |
| PubMed ID: 7380831 |
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| Polmar SH, Stern RC, Schwartz AL, Wetzler EM, Chase PA, Hirschhorn R, Enzyme replacement therapy for adenosine deaminase deficiency and severe combined immunodeficiency. N Engl J Med295:1337-43 1976 |
| PubMed ID: 980079 |
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| Hirschhorn R, Beratis N, Rosen FS, Parkman R, Stern R, Polmar S, Adenosine-deaminase deficiency in a child diagnosed prenatally. Lancet1:73-75 1975 |
| PubMed ID: 46025 |
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| Polmar SH, Wetzler EM, Stern RC, Hirschhorn R, Restoration of in-vitro lymphocyte responses with exogenous adenosine deaminase in a patient with severe combined immunodeficiency. Lancet2:743-6 1975 |
| PubMed ID: 52774 |
| dbSNP |
dbSNP ID: 19388 |
| 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 |
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 |
| Substrate |
None specified |
| Subcultivation Method |
trypsin-EDTA |
| Supplement |
- |
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