GM11411
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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White
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Ethnicity
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AMISH
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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, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
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| GENE MAPPING & DOSAGE STUDIES - Y CHROMOSOME |
PCR analysis of DNA from this cell culture gave a positive result with a primer for Yq11, DYS227. |
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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; 0.1% activity. |
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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; 0.2% activity. |
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| Gene |
ADA |
| Chromosomal Location |
20q13.11 |
| Allelic Variant 1 |
608958.0016; SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-NEGATIVE, DUE TO ADENOSINE DEAMINASE DEFICIENCY |
| Identified Mutation |
GLY216ARG; In a patient, GM11411, with very severe combined immunodeficiency, Hirschhorn et al. [Am J Hum Genet 49: 878 (1991)] identified a transition of G-646 to A at a CG dinucleotide, predicting a glycine-to-arginine substitution at codon 216 of the ADA protein.The patient was homozygous, the offspring of consanguineous Amish parents from eastern Pennsylvania. Onset of symptoms was at 3 days of age with respiratory distress from pneumonia unresponsive to antibiotics. |
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| Gene |
ADA |
| Chromosomal Location |
20q13.11 |
| Allelic Variant 2 |
608958.0016; SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-NEGATIVE, DUE TO ADENOSINE DEAMINASE DEFICIENCY |
| Identified Mutation |
GLY216ARG; In a patient, GM11411, with very severe combined immunodeficiency, Hirschhorn et al. [Am J Hum Genet 49: 878 (1991)] identified a transition of G-646 to A at a CG dinucleotide, predicting a glycine-to-arginine substitution at codon 216 of the ADA protein.The patient was homozygous, the offspring of consanguineous Amish parents from eastern Pennsylvania. Onset of symptoms was at 3 days of age with respiratory distress from pneumonia unresponsive to antibiotics. |
| Remarks |
Clinically affected; Amish; onset at age 3 days with respiratory distress, pneumonia, and lymphopenia; remained profoundly lymphopenic during first 6 weeks of life with few mature T or B cells and with 23% mononuclear cells bearing NK markers; at one month of age both IgA and IgM were non-detectable and there was absence of proliferative response of lymphocytes to the mitogens PHA, Con A, or PWM; chondro-osseous dysplasia; ADA activity in erythrocytes was less than 0.2% of normal; ADA activity in lymphoblast culture was less than 0.1% of normal; erythrocyte deoxy ATP was markedly elevated; donor subject is homozygous for a G>A transition at nucleotide 646 in exon 7 of the ADA gene [646G>A] resulting in a substitution of arginine for glycine at codon 216 [Gly216Arg (G216R)]; parents are GM11412 and GM11413. |
| Lamontagne RJ, Soldan SS, Su C, Wiedmer A, Won KJ, Lu F, Goldman AR, Wickramasinghe J, Tang HY, Speicher DW, Showe L, Kossenkov AV, Lieberman PM, A multi-omics approach to Epstein-Barr virus immortalization of B-cells reveals EBNA1 chromatin pioneering activities targeting nucleotide metabolism PLoS pathogens17:e1009208 2020 |
| PubMed ID: 33497421 |
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| Zhong XZ1, Zou Y1, Sun X1,2, Dong G1, Cao Q1, Pandey A3, Rainey JK3,4, Zhu X2, Dong XP5., Inhibition of Transient Receptor Potential Channel Mucolipin-1 (TRPML1) by Lysosomal Adenosine Involved in Severe Combined Immunodeficiency Diseases. J Biol Chem.292(8):3445-3455 2017 |
| PubMed ID: 28087698 |
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| Hirschhorn R, Ellenbogen A, Tzall SHirschhorn, Five missense mutations at the adenosine deaminase locus (ADA) detected by altered restriction fragments and their frequency in ADA--patients with severe combined immunodeficiency (ADA-SCID). Am J Hum Genet42:201-7 1992 |
| PubMed ID: 1346349 |
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| Hirschhorn R, Chakravarti V, Puck J, Douglas SD, Homozygosity for a newly identified missense mutation in a patient with very severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID). Am J Hum Genet49:878-85 1991 |
| PubMed ID: 1680289 |
| dbSNP |
dbSNP ID: 11556 |
| 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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