A novel point mutation (I137T) in the conserved 5-phosphoribosyl-1-pyrophosphate binding motif of hypoxanthine-guanine phosphoribosyltransferase (HPRTJerusalem) in a variant of Lesch-Nyhan syndrome

Mol Genet Metab. 2003 Feb;78(2):158-61. doi: 10.1016/s1096-7192(03)00002-7.


We identified a novel point mutation (I137T) in the hypoxanthine-guanine phosphoribosyltransferase (HPRT; EC encoding gene, in a patient with partial deficiency of the enzyme (variant of Lesch-Nyhan syndrome). The mutation, ATT to ACT, resulting in substitution of isoleucine to threonine, occurred at codon 137 (exon 6), which is within the region encoding the binding site for 5-phosphoribosyl-1-pyrophosphate (PRPP). We suggest the mechanism by which the mutation-induced structural alteration of HPRT reduced the affinity of the enzyme for PRPP.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites
  • Child, Preschool
  • DNA Primers
  • Female
  • Humans
  • Hypoxanthine Phosphoribosyltransferase / metabolism*
  • Lesch-Nyhan Syndrome / genetics*
  • Male
  • Models, Molecular
  • Phosphoribosyl Pyrophosphate / metabolism*
  • Point Mutation*
  • Pregnancy


  • DNA Primers
  • Phosphoribosyl Pyrophosphate
  • Hypoxanthine Phosphoribosyltransferase