title: Molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in ten subjects determined by direct sequencing of amplified transcripts.
abstract: Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is an inborn error of purine metabolism. Mutant HPRT gene sequences from patients deficient in enzyme activity 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 polymerase 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. Several of these mutations map near previously identified HPRT variants, and are located in evolutionarily conserved regions of the molecule.
authors.affiliation: Department of Internal Medicine, Rackham Arthritis Research Unit, University of Michigan Multipurpose Arthritis Center, Ann Arbor 48109.
authors.forename: B L
authors.initials: BL
authors.lastname: Davidson
authors.forename: S A
authors.initials: SA
authors.lastname: Tarlé
authors.forename: T D
authors.initials: TD
authors.lastname: Palella
authors.forename: W N
authors.initials: WN
authors.lastname: Kelley
mesh_terms: D000595:Amino Acid Sequence; D004247:DNA / Q000032:analysis; D005784:Gene Amplification; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency* / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D014158:Transcription, Genetic
chemical_list: D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase