A 13 base pair deletion in exon 1 of HPRT Illinois forms a functional GUG initiation codon

Abstract

More than 50 mutations in the human hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus have been described, yet only 2 alter the AUG initiation codon. One, variant HPRT 1151 , results in Lesch-Nyhan syndrome (LNS), and the other, HPRT Illinois , results in partial HPRT deficiency. Although previously undetectable, we used a sensitive gel assay to demonstrate that HPRT Illinois is not only active, but has a native Mr indistinguishable from normal. Confirmatory evidence of activity and native Mr is demonstrated following transfection of HPRT cells with expression plasmids containing cDNA sequences representing HPRT Illinois . These data provide support for the hypothesis that patient RT, or variant HPRT Illinois , is spared manifestations of the LNS as a result of translation at the newly formed GUG initiation codon.