A 13 BASE-PAIR DELETION IN EXON-1 OF HPRT(ILLINOIS) FORMS A FUNCTIONAL GUG INITIATION CODON

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,eel 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.