Skip to main content
SpringerLink
Log in

The Genetic Basis of HGPRT Deficiency

  • Conference paper
Molecular Genetics, Biochemistry and Clinical Aspects of Inherited Disorders of Purine and Pyrimidine Metabolism

  • 109 Accesses

Abstract

Complete deficiency of the purine salvage enzyme hypoxanthine guanine phosphoribosyltransferase (HGPRT) results in the Lesch-Nyhan syndrome, a disease characterized by hyperuricemia, gout, and a bizarre tendency to self-mutilation, choreoathetosis, and other neurological dysfunction [1]. Partial deficiency of HGPRT is characterized by gout, hyperuricemia, and hyperuricaciduria and is known as the Kelley-Seegmiller syndrome [2]. The gene encoding HGPRT is located on the long arm of the X-chromosome and most often transmitted in a classic X-linked manner with an incidence of 1:100 000 live births. However, spontaneous cases do occur and at least one case of an affected female has been reported [3].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Lesch M, Nyhan WL (1964) A familial disorder of uric acid metabolism and central nervous system function. Am J Med 36: 561–570

    Article  PubMed  CAS  Google Scholar 

  2. Kelley WN, Rosenbloom FM, Henderson JF, Seegmiller JE (1967) A specific enzyme defect in gout associated with overproduction of uric acid. Proc Natl Acad Sci 57: 1735–1739

    Article  PubMed  CAS  Google Scholar 

  3. Ogasawara N, Stout JT; Goto H, Sonta S, Matsumoto A, Caskey CT(1989) Molecular analysis of a female Lesch-Nyhan patient. J Clin Invest 84: 1024–1027

    Google Scholar 

  4. Davidson BL, Palella TD, Kelly WN (1988) Human hypoxanthine-guanine phosphoribosyl transferase: a single nucleotide substitution in cDNA clone isolated from a patient with Lesch-Nyhan syndrome. Gene 68: 85–91

    Article  PubMed  CAS  Google Scholar 

  5. Wilson JM, Stout JT, PalellaTD, Davidson BL, Kelley WN, Caskey CT (1986) A molecular survey of hypoxanthine-guanine phosphoribosyl-transferase deficiency in man. J Clin Invest 77: 188–195

    Article  PubMed  CAS  Google Scholar 

  6. Gibbs RA, Nguyen P, McBride LJ, Koepf SM, Caskey CT (1989) Identification of mutations leading to Lesch-Nyhan syndrome by automated direct DNA sequencing of in vitro amplified cDNA. Proc Natl Acad Sci 86: 1919–1923

    Article  PubMed  CAS  Google Scholar 

  7. 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: 499–501

    Article  PubMed  CAS  Google Scholar 

  8. Davidson BL, Pashmforoush M, Kelley WN, PalellaTD (1989) Human hypoxanthineguanine phosphoribosyltransferase deficiency. J Biol Chem 264: 520–525

    PubMed  CAS  Google Scholar 

  9. Davidson BL, Tarle SA, van Antwerp M, Gibbs DA, Watts RWE, Kelley WN, Palella TD (1991) Identification of 17 independent mutations responsible for human hypoxanthineguanine phosphoribosyltransferase ( HGPRT) deficiency. Am J Hum Genet 48: 951–958

    Google Scholar 

  10. Yang TP, Stout JT, Konecki DS, Patel PI, Alford RL, Caskey CT (1988) Spontaneous reversion of novel Lesch-Nyhan mutation by HGPRT gene rearrangement. Somat Cell Mol Genet 14: 293–303

    Article  PubMed  CAS  Google Scholar 

  11. Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, et al (1988) Primer directed enzymatic amplification of DNA with thermostable DNA polymerase. Science 239: 487–491

    Article  PubMed  CAS  Google Scholar 

  12. Goodenow M, Huet T, Saurin W, Kwok S, Wain-Hobson S (1989) HIV1 isolates are rapidly evolving quasispecies: evidence for viral mixtures and preferred nucleotide substitutions. J Acquir Immune Def Synd 2: 344–352

    CAS  Google Scholar 

  13. Chou PY, Fasman GD (1978) Empirical predictions of protein conformation. Ann Rev Biochem 47: 251–276

    Article  PubMed  CAS  Google Scholar 

  14. Hopp TP, Woods KR (1981) Prediction of protein antigenic determinants from amino acid sequences. Proc Natl Acad Sci USA 78: 3824–3828

    Article  PubMed  CAS  Google Scholar 

  15. Monnat RJ Jr., ChiaverottiTM, Hackmann AFM (1991) Molecular analysis of human HGPRT gene deletions and duplications. Adv Exp Med Biol 309 B: 113–116

    Google Scholar 

  16. Kennett RH (1979) Cell fusion, in Methods in Enzymology, Vol 52, Colowick SP, Kaplan NO eds. pp 345–359 Academic Press, New York

    Google Scholar 

  17. Becerra SP, Rose JA, Hardy M, Baroudy BM, Anderson CW (1985) Direct mapping of adeno-associated virus capsid proteins B and C: a possible ACG initiation codon. Proc Natl Acad Sci USA 82: 7919–7923

    Article  PubMed  CAS  Google Scholar 

  18. Curran J, and Kolakofsky D (1988) Ribosomal initiation from an ACG codon in the Sendai virus P/C mRNA. Embo Journal 7: 245–251

    PubMed  CAS  Google Scholar 

  19. Acland P, Dixon M, Peters G, Dickson C (1990) Subcellular fate of the Int-2 oncoprotein is determined by choice of initiation codon Nature 343: 662–665

    CAS  Google Scholar 

  20. Sugihara H, Andrisani V, Salvaterra PM (1990) Drosophila choline acetyltransferase uses a non-AUG initiation codon and full length RNAis inefficiently translated. J Biol Chem 265: 21714–21719

    PubMed  CAS  Google Scholar 

  21. Lemair P, Vesque C, Schmitt J, Stunnenberg H, Frank R, Charnay P (1990)The seruminducible mouse gene Krox-24 encodes a sequence specific transcriptional activator. Mol Cell Biol 10: 3456–3467

    Google Scholar 

  22. Prats A, Wang G, Darlix J (1989) CUG initiation codon used for the synthesis of a cell surface antigen coded by the murine leukemia virus. J Mol Biol 205: 3633–372

    Article  Google Scholar 

  23. Peabody DS (1987) Translation initiation at an ACG triplet in mammalian cells. J Biol Chem 262: 11847–11851

    PubMed  CAS  Google Scholar 

  24. Florkiewicz RZ, Sommer A (1989) Human basic fibroblast growth factor gene encodes four polypeptides: three initiate translation from non-AUG codons. Proc Natl Acad Sci USA 86: 3978–3981

    Article  PubMed  CAS  Google Scholar 

  25. Taira M, IizasaT, Shimada H, Kudoh J, Shimuzu N, Tatibana M (1990) A human testis-specific mRNA for phosphoribosylpyrophosphate synthetase that initiates from a non- AUG codon. J Biol Chem 265: 16491–16497

    CAS  Google Scholar 

  26. Prats H (1989) High molecular mass forms of basic fibroblast growth factor are initiated by alternative CUG codons. Proc Natl Acad Sci USA 80: 1836–1840

    Article  Google Scholar 

  27. Kozak M (1986) Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell 44: 283–292

    Article  PubMed  CAS  Google Scholar 

  28. Kozak M (1987) At least six nucleotides precending the AUG initiator codon enhance translation in mammalian cells. J Mol Biol 196: 947–950

    Article  PubMed  CAS  Google Scholar 

  29. Kozak M (1989) Context effects and inefficient initiation at non-AUG codons in eukaryotic cell-free translation systems. Mol Cell Biol 9: 5073–5080

    PubMed  CAS  Google Scholar 

  30. Kozak M (1990) Downstream secondary structure facilitates recognition of initiator codons by eukaryotic ribosomes. Proc Natl Acad Sci USA 87: 8301–8305

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. B. L. Davidson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. J. Roessler
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Medizinische Poliklinik, Universität München, Pettenkoferstr. 8 a, 80336, München, Germany

    Ursula Gresser

Rights and permissions

Reprints and permissions

Copyright information

© 1993 Springer Verlag, Berlin Heidelberg

About this paper

Cite this paper

Davidson, B.L., Roessler, B.J. (1993). The Genetic Basis of HGPRT Deficiency. In: Gresser, U. (eds) Molecular Genetics, Biochemistry and Clinical Aspects of Inherited Disorders of Purine and Pyrimidine Metabolism. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-84962-6_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-84962-6_5

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-84964-0

  • Online ISBN: 978-3-642-84962-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation