The Genetic Basis of APRT Deficiency

We have determined the molecular basis of adenine phosphoribosyltransferase (APRT) deficiency in 27 families. The APRT gene from each patient was amplified by the polymerase chain reaction, subcloned into M13mp18, and sequenced completely. Selected regions of the amplified fragment were also sequenced directly. DNA samples were also analyzed by Sph I and Taq I digestions and Southern blotting. A total of 18 different mutations alleles were identified. The mutations were nonrandomly distributed and suggested the presence of hot spots. At least three mutations appeared to have common ancestral origins. The paucity of intron or exon polymorphisms in these patients confirmed our previous studies that the APRT gene is highly conserved.