Search tips
Search criteria 


Logo of jcinvestThe Journal of Clinical Investigation
J Clin Invest. 1988 March; 81(3): 945–950.
PMCID: PMC442550

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


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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Kelley WN, Levy RI, Rosenbloom FM, Henderson JF, Seegmiller JE. Adenine phosphoribosyltransferase deficiency: a previously undescribed genetic defect in man. J Clin Invest. 1968 Oct;47(10):2281–2289. [PMC free article] [PubMed]
  • Wilson JM, O'Toole TE, Argos P, Shewach DS, Daddona PE, Kelley WN. Human adenine phosphoribosyltransferase. Complete amino acid sequence of the erythrocyte enzyme. J Biol Chem. 1986 Oct 15;261(29):13677–13683. [PubMed]
  • Tischfield JA, Ruddle FH. Assignment of the gene for adenine phosphoribosyltransferase to human chromosome 16 by mouse-human somatic cell hybridization. Proc Natl Acad Sci U S A. 1974 Jan;71(1):45–49. [PubMed]
  • Murray AM, Drobetsky E, Arrand JE. Cloning the complete human adenine phosphoribosyl transferase gene. Gene. 1984 Nov;31(1-3):233–240. [PubMed]
  • Stambrook PJ, Dush MK, Trill JJ, Tischfield JA. Cloning of a functional human adenine phosphoribosyltransferase (APRT) gene: identification of a restriction fragment length polymorphism and preliminary analysis of DNAs from APRT-deficient families and cell mutants. Somat Cell Mol Genet. 1984 Jul;10(4):359–367. [PubMed]
  • Broderick TP, Schaff DA, Bertino AM, Dush MK, Tischfield JA, Stambrook PJ. Comparative anatomy of the human APRT gene and enzyme: nucleotide sequence divergence and conservation of a nonrandom CpG dinucleotide arrangement. Proc Natl Acad Sci U S A. 1987 May;84(10):3349–3353. [PubMed]
  • Hidaka Y, Tarlé SA, O'Toole TE, Kelley WN, Palella TD. Nucleotide sequence of the human APRT gene. Nucleic Acids Res. 1987 Nov 11;15(21):9086–9086. [PMC free article] [PubMed]
  • Srivastava SK, Villacorte D, Beutler E. Correlation between adenylate metabolizing enzymes and adenine nucleotide levels of erythrocytes during blood storage in various media. Transfusion. 1972 May-Jun;12(3):190–197. [PubMed]
  • Fox IH. Purine enzyme abnormalities: a four year experience. Adv Exp Med Biol. 1977;76A:265–269. [PubMed]
  • Johnson LA, Gordon RB, Emmerson BT. Adenine phosphoribosyltransferase: a simple spectrophotometric assay and the incidence of mutation in the normal population. Biochem Genet. 1977 Apr;15(3-4):265–272. [PubMed]
  • Kamatani N, Terai C, Kuroshima S, Nishioka K, Mikanagi K. Genetic and clinical studies on 19 families with adenine phosphoribosyltransferase deficiencies. Hum Genet. 1987 Feb;75(2):163–168. [PubMed]
  • Joost J, Doppler W. 2,8-dihydroxyadenine stone in children. Urology. 1982 Jul;20(1):67–70. [PubMed]
  • Witten FR, Morgan JW, Foster JG, Glenn JF. 2,8-dihydroxyadenine urolithiasis: review of the literature and report of a case in the United States. J Urol. 1983 Nov;130(5):938–942. [PubMed]
  • Fujimori S, Akaoka I, Sakamoto K, Yamanaka H, Nishioka K, Kamatani N. Common characteristics of mutant adenine phosphoribosyltransferases from four separate Japanese families with 2,8-dihydroxyadenine urolithiasis associated with partial enzyme deficiencies. Hum Genet. 1985;71(2):171–176. [PubMed]
  • Hidaka Y, Palella TD, O'Toole TE, Tarlé SA, Kelley WN. Human adenine phosphoribosyltransferase. Identification of allelic mutations at the nucleotide level as a cause of complete deficiency of the enzyme. J Clin Invest. 1987 Nov;80(5):1409–1415. [PMC free article] [PubMed]
  • Nobori T, Kamatani N, Mikanagi K, Nishida Y, Nishioka K. Establishment and characterization of B cell lines from individuals with various types of adenine phosphoribosyltransferase deficiencies. Biochem Biophys Res Commun. 1986 Jun 30;137(3):998–1005. [PubMed]
  • Wilson JM, Baugher BW, Landa L, Kelley WN. Human hypoxanthine-guanine phosphoribosyltransferase. Purification and characterization of mutant forms of the enzyme. J Biol Chem. 1981 Oct 25;256(20):10306–10312. [PubMed]
  • Wilson JM, Baugher BW, Mattes PM, Daddona PE, Kelley WN. Human hypoxanthine-guanine phosphoribosyltransferase. Demonstration of structural variants in lymphoblastoid cells derived from patients with a deficiency of the enzyme. J Clin Invest. 1982 Mar;69(3):706–715. [PMC free article] [PubMed]
  • Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. [PubMed]
  • Thomas PS. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. [PubMed]
  • Feinberg AP, Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. [PubMed]
  • Young RA, Davis RW. Efficient isolation of genes by using antibody probes. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1194–1198. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PubMed]
  • Chou PY, Fasman GD. Empirical predictions of protein conformation. Annu Rev Biochem. 1978;47:251–276. [PubMed]
  • Chou PY, Fasman GD. Prediction of the secondary structure of proteins from their amino acid sequence. Adv Enzymol Relat Areas Mol Biol. 1978;47:45–148. [PubMed]
  • Hershey HV, Taylor MW. Nucleotide sequence and deduced amino acid sequence of Escherichia coli adenine phosphoribosyltransferase and comparison with other analogous enzymes. Gene. 1986;43(3):287–293. [PubMed]
  • Gibbs RA, Caskey CT. Identification and localization of mutations at the Lesch-Nyhan locus by ribonuclease A cleavage. Science. 1987 Apr 17;236(4799):303–305. [PubMed]
  • Chehab FF, Honig GR, Kan YW. Spontaneous mutation in beta-thalassaemia producing the same nucleotide substitution as that in a common hereditary form. Lancet. 1986 Jan 4;1(8471):3–5. [PubMed]
  • Youssoufian H, Kazazian HH, Jr, Phillips DG, Aronis S, Tsiftis G, Brown VA, Antonarakis SE. Recurrent mutations in haemophilia A give evidence for CpG mutation hotspots. Nature. 324(6095):380–382. [PubMed]
  • Ledley FD, Woo SL. Molecular basis of alpha 1-antitrypsin deficiency and its potential therapy by gene transfer. J Inherit Metab Dis. 1986;9 (Suppl 1):85–91. [PubMed]
  • DiLella AG, Marvit J, Brayton K, Woo SL. An amino-acid substitution involved in phenylketonuria is in linkage disequilibrium with DNA haplotype 2. Nature. 327(6120):333–336. [PubMed]
  • Tsuji S, Choudary PV, Martin BM, Stubblefield BK, Mayor JA, Barranger JA, Ginns EI. A mutation in the human glucocerebrosidase gene in neuronopathic Gaucher's disease. N Engl J Med. 1987 Mar 5;316(10):570–575. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation