Lesch-Nyhan Syndrome due to a Single Nucleotide Change in the Hypoxanthine-Guanine Phosphoribosyltransferase Gene (HPRT Yale)
Hypoxanthine-guanine phosphoribosyltransferase (HPRT: E.C. 220.127.116.11) is a purine salvage enzyme that catalyzes the conversion of hypoxanthine and guanine to their respective nucleotides. Complete deficiency of HPRT is associated with the Lesch-Nyhan syndrome, an X-linked disorder manifested by hyperuricemia, mental retardation, choreoathetosis and compulsive self-mutilation.1 Partial deficiency of this enzyme leads to overproduction of uric acid, which results in the development of a severe form of gout.2 By sequence analysis of tryptic peptides, single amino acid substitutions have been defined in four HPRT variants.3 However, most HPRT deficient subjects have insufficient amounts of mutant protein for this type of analysis. Furthermore, the HPRT gene is very large (44 kb) and Southern blot analyses of genomic DNA from most HPRT deficient subjects are normal.4, 5 On the other hand, more than 80% of HPRT deficient subjects have normal quantities of HPRT specific messenger RNA (mRNA).5 These characteristics, together with available techniques for cDNA cloning, provide the necessary rationale and tools for the identification of mutations which leads to dysfunctional HPRT.
KeywordsSingle Amino Acid Substitution Specific Oligonucleotide Primer Dideoxynucleotide Chain Termination Method Respective Nucleotide Span Amino Acid Residue
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