title: An asymptomatic germline missense base substitution in the hypoxanthine phosphoribosyltransferase (HPRT) gene that reduces the amount of enzyme in humans.
abstract: A 40-year-old normouricemic (5.5 mg/dl) male showed 46% hemolysate and 37% lymphoblast hypoxanthine phosphoribosyltransferase (HPRT) activities but was otherwise completely free of symptoms. His genomic DNA and cDNA had a missense base substitution (CAT-to-CGT in codon 60) leading to the amino-acid substitution His-to-Arg. Western blot analysis revealed that the amount of HPRT protein in lymphoblasts from this individual was 25%-50% of normal cells, suggesting that the decrease in the amount of enzyme protein was responsible for the partial deficiency. This provides the first clear evidence that a genomic missense mutation at the HPRT locus leads to a decrease in the amount of the enzyme protein but that otherwise it has no evident adverse effects in the hemizygote (asymptomatic mutation).
authors.affiliation: Second Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Fujimori
authors.forename: R
authors.initials: R
authors.lastname: Sakuma
authors.forename: N
authors.initials: N
authors.lastname: Yamaoka
authors.forename: M
authors.initials: M
authors.lastname: Hakoda
authors.forename: H
authors.initials: H
authors.lastname: Yamanaka
authors.forename: N
authors.initials: N
authors.lastname: Kamatani
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001120:Arginine; D001402:B-Lymphocytes / Q000201:enzymology; D015153:Blotting, Western; D017931:DNA Primers; D005091:Exons; D006639:Histidine; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000097:blood / Q000172:deficiency* / Q000235:genetics*; D008297:Male; D017354:Point Mutation
chemical_list: D017931:DNA Primers; D006639:Histidine; D001120:Arginine; D007041:Hypoxanthine Phosphoribosyltransferase