A point mutation responsible for human erythrocyte AMP deaminase deficiency.

A point mutation of C to T on the human erythrocyte AMP deaminase gene (AMPD-3) has been identified by molecular analysis of the genetic materials from the enzyme deficient individuals. Four separate DNA fragments covering the entire coding region of AMPD-3 cDNA were amplified using polymerase chain reaction (PCR) technique and sequenced directly. The same point mutation was detected in both of the two B-lymphoblast cell lines derived from the complete deficiency of human erythrocyte AMP deaminase: a single nucleotide substitution of C to T resulted in an amino acid change of Arg to Cys at the codon 573. The analysis of genomic DNA demonstrated that two individuals with complete deficiency were homozygous for the detected mutation, and two individuals with partial deficiency were diagnosed as heterozygous. This mis-sense mutation reads to a catalytically inactive enzyme.