title: One adenosine deaminase allele in a patient with severe combined immunodeficiency contains a point mutation abolishing enzyme activity.
abstract: We have cloned and sequenced an adenosine deaminase (ADA) gene from a patient with severe combined immunodeficiency (SCID) caused by inherited ADA deficiency. Two point mutations were found, resulting in amino acid substitutions at positions 80 (Lys to Arg) and 304 (Leu to Arg) of the protein. Hybridization experiments with synthetic oligonucleotide probes showed that the determined mutations are present in both DNA and RNA from the ADA-SCID patient. In addition, wild-type sequences could be detected at the same positions, indicating a compound heterozygosity. Studies with ADA expression clones mutagenized in vitro showed that the mutation at position 304 is responsible for ADA inactivation.
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics*; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D004262:DNA Restriction Enzymes; D005796:Genes; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology / Q000235:genetics*; D007930:Leucine; D008239:Lysine; D051379:Mice; D009154:Mutation; D009700:Nucleoside Deaminases / Q000235:genetics*; D010957:Plasmids; D013045:Species Specificity
chemical_list: D001120:Arginine; D004262:DNA Restriction Enzymes; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase; D007930:Leucine; D008239:Lysine