Molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in ten subjects determined by direct sequencing of amplified transcripts.

Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is an inborn error of purine metabolism.Mutant HPRT gene sequences from patients deficient in enzyme activ- ity have previously been characterized by cDNA cloning or amino acid sequencing techniques.The presence of HPRT- specific mRNA in nearly all deficient subjects, as well as the small size of the HPRT mRNA (1,400 bp), make the polymer- ase chain reaction (PCR) an alternative for the identification of mutations at this locus.In this report we use the PCR to identify previously undetermined mutations in HPRT mRNA from B lymphoblasts derived from 10 deficient individuals.Six of these variants contain single point mutations, three contain deletions, and one contains a single nucleotide insertion.Sev- eral of these mutations map near previously identified HPRT variants, and are located in evolutionarily conserved regions of the molecule.causes the Lesch-Nyhan syndrome, which is characterized by hyperuricemia, hyperuricaciduria, and severe neurologic dys- function consisting of hyperreflexia, choreathetosis, mental retardation, and self-mutilation (1, 2).Patients with partial deficiency have severe gout and uric acid nephrolithiasis, but are usually spared neurologic dysfunction (3).Early reports of HPRT deficiency demonstrated heteroge- neity of kinetic and electrophoretic properties of the protein