Human adenine phosphoribosyltransferase deficiency. Demonstration of a single mutant allele common to the Japanese

J Clin Invest. 1988 Mar;81(3):945-50. doi: 10.1172/JCI113408.


Complete adenine phosphoribosyltransferase (APRT) deficiency causes 2,8-dihydroxyadenine urolithiasis. In previous reports, analysis of the kinetic properties of APRT from APRT-deficient Japanese subjects revealed strikingly similar abnormalities suggesting a distinct "Japanese-type" mutation. In this paper, we report studies of 11 APRT-deficient lymphoblast cell lines. Nucleotide sequence analysis of APRT genomic DNA from WR2, a Japanese-type homozygote, identified a T to C substitution in exon 5, giving rise to the substitution of threonine for methionine at position 136. RNase mapping analysis confirmed this mutation in WR2 and revealed that six other Japanese-type homozygotes carry the same mutation on at least one allele. The remaining Japanese subject, who does not express the Japanese-type phenotype, did not demonstrate this mutation. Southern blot analysis showed that all seven Japanese-type subjects were confined to one TaqI restriction fragment length polymorphism (RFLP) haplotype. These studies provide direct evidence for the nature of the mutation in the Japanese-type APRT deficiency.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenine Phosphoribosyltransferase / deficiency*
  • Adenine Phosphoribosyltransferase / genetics
  • Alleles*
  • Amino Acid Sequence
  • Base Sequence
  • Cloning, Molecular
  • Humans
  • Japan / ethnology
  • Lymphocytes / enzymology
  • Mutation*
  • Pentosyltransferases / deficiency*
  • Phenotype
  • White People


  • Pentosyltransferases
  • Adenine Phosphoribosyltransferase