Human Genetics

, Volume 88, Issue 6, pp 695–696 | Cite as

The point mutation of hypoxanthine-guanine phosphoribosyltransferase (HPRTEdinburgh) and detection by allele-specific polymerase chain reaction

  • Therese Lightfoot
  • Rahul Joshi
  • George Nuki
  • Floyd F. Snyder
Short Communications


The change in DNA responsible for partial hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency in three brothers has been determined by polymerase chain amplification and sequencing. An A-to-G substitution at base 155 in exon 3 predicts a change in aspartic acid 52 to glycine. Allele-specific polymerase chain amplification verified the presence of the mutation in genomic DNA and provides a means of direct diagnostic assay.


Polymerase Chain Reaction Internal Medicine Glycine Metabolic Disease Point Mutation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Chou PY, Fasman GD (1978) Empirical predictions of protein conformation. Annu Rev Biochem 47:251–276Google Scholar
  2. Davidson BL, Tarle SA, Van Antwerp M, Gibbs DA, Watts RWE, Kelley WN, Palella TD (1991) Identification of 17 independent mutations responsible for human hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency. Am J Hum Genet 48:951–958Google Scholar
  3. Gubler U, Hoffman BJ (1983) A simple and very efficient method for generating cDNA libraries. Gene 25:263–269Google Scholar
  4. Jolly DJ, Okayama H, Berg P, Esty AC, Filpula C, Bohlen P, Johnson GG, Shively JE, Hunkapillar T, Friedmann T (1983) Isolation and characterization of a full-length expressible cDNA for human hypoxanthine phosphoribosyltransferase. Proc Natl Acad Sci USA 80:477–481Google Scholar
  5. Kelley WN, Rosenbloom FM, Henderson JF, Seegmiller JE (1967) A specific enzyme defect in gout is associated with overproduction of uric acid. Proc Natl Acad Sci USA 57:1735–1739Google Scholar
  6. Patel PI, Nussbaum RL, Framson PE, Ledbetter DH, Caskey CT, Chinault AC (1984) Organization of the HPRT gene and related sequences in the human genome. Somatic Cell Mol Genet 10:483–493Google Scholar
  7. Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA (1988) Primer directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239:487–491Google Scholar
  8. Sanger F, Nicklen S, Coulsen AR (1977) DNA sequencing with chain terminating inhibitors. Proc Natl Acad Sci USA 74:5463–5467Google Scholar
  9. Simpson D, Crosby RM, Skopek TR (1988) A method for specific cloning and sequencing of human HPRT cDNA for mutation analysis. Biochem Biophys Res Commun 151:487–492Google Scholar
  10. Snyder FF, Joyce JE, Carter-Edwards T, Joshi R, Rylance HL, Wallace RC, Nuki G (1989) Hypoxanthine-guanine phosphoribosyltransferase deficiency in three brothers with gout: characterization of a variant, HPRTEEdinburgh, having altered isoelectric point, increased thermal lability and normal levels of messenger RNA. J Inherited Metab Dis 12:390–402Google Scholar
  11. Tarle SA, Davidson BL, Wu VC, Zidar FJ, Seegmiller JE, Kelley WN, Palella TD (1991) Determination of the mutations responsible for the Lesch-Nyhan Syndrome in 17 subjects. Genomics 10:499–501Google Scholar
  12. Wilson JM, Kobayashi R, Fox IH, Kelley WN (1983) Human hypoxanthine-guanine phosphoribosyltransferase: molecular abnormality in a mutant form of the enzyme (HPRTToronto). J Biol Chem 258:6458–6460Google Scholar
  13. Wolf H, Modrow S, Motz M, Jameson BA, Herman G, Fortsch B (1988) An integrated family of amino acid sequence analysis programs. Comput Appl Biosci 4:187–191Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Therese Lightfoot
    • 1
  • Rahul Joshi
    • 1
  • George Nuki
    • 2
  • Floyd F. Snyder
    • 1
  1. 1.Department of Paediatrics and Department of Medical BiochemistryUniversity of CalgaryCalgaryCanada
  2. 2.Rheumatic Disease Unit, Department of MedicineUniversity of Edinburgh, Northern General HospitalEdinburghUK

Personalised recommendations