title: Adenosine deaminase (ADA) deficiency in cells derived from humans with severe combined immunodeficiency is due to an aberration of the ADA protein.
abstract: In order to determine the molecular basis of adenosine deaminase (ADA) deficiency in cells derived from patients with severe combined immunodeficiency (SCID) disease, we used a human ADA cDNA clone (1) to analyse the organization and transcription of the ADA gene in both normal and ADA-SCID cells. In five lymphoblastoid ADA-SCID cell lines we could detect no deletions or rearrangements in the ADA gene and its flanking sequences. Furthermore, synthesis and processing of ADA mRNA appeared to be normal in the ADA-SCID cells, and ADA-specific mRNA from two ADA-SCID cells could be translated in vitro into a protein with the molecular weight of normal ADA; this protein, however, could hardly be precipitated with an ADA antiserum. The results indicate that in these two ADA-SCID cell lines, the lack of ADA activity is not due to transcriptional or translational defects, but to subtle changes in the configuration of the protein affecting both its enzymatic and immunological characteristics.
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency* / Q000235:genetics; D002460:Cell Line; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D004247:DNA / Q000032:analysis; D005796:Genes; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology* / Q000235:genetics; D009693:Nucleic Acid Hybridization; D009700:Nucleoside Deaminases / Q000172:deficiency*; D011061:Poly A / Q000235:genetics; D012313:RNA / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger; D011061:Poly A; D012313:RNA; D004247:DNA; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase