title: Human adenine phosphoribosyltransferase deficiency. Demonstration of a single mutant allele common to the Japanese.
abstract: Complete adenine phosphoribosyltransferase (APRT) deficiency causes 2,8-dihydroxyadenine urolithiasis. In previous reports, analysis of the kinetic properties of APRT from APRT-deficient Japanese subjects revealed strikingly similar abnormalities suggesting a distinct "Japanese-type" mutation. In this paper, we report studies of 11 APRT-deficient lymphoblast cell lines. Nucleotide sequence analysis of APRT genomic DNA from WR2, a Japanese-type homozygote, identified a T to C substitution in exon 5, giving rise to the substitution of threonine for methionine at position 136. RNase mapping analysis confirmed this mutation in WR2 and revealed that six other Japanese-type homozygotes carry the same mutation on at least one allele. The remaining Japanese subject, who does not express the Japanese-type phenotype, did not demonstrate this mutation. Southern blot analysis showed that all seven Japanese-type subjects were confined to one TaqI restriction fragment length polymorphism (RFLP) haplotype. These studies provide direct evidence for the nature of the mutation in the Japanese-type APRT deficiency.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109.
authors.forename: Y
authors.initials: Y
authors.lastname: Hidaka
authors.forename: S A
authors.initials: SA
authors.lastname: Tarlé
authors.forename: S
authors.initials: S
authors.lastname: Fujimori
authors.forename: N
authors.initials: N
authors.lastname: Kamatani
authors.forename: W N
authors.initials: WN
authors.lastname: Kelley
authors.forename: T D
authors.initials: TD
authors.lastname: Palella
mesh_terms: D000228:Adenine Phosphoribosyltransferase / Q000172:deficiency* / Q000235:genetics; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D006801:Humans; D007564:Japan / Q000208:ethnology; D008214:Lymphocytes / Q000201:enzymology; D009154:Mutation; D010430:Pentosyltransferases / Q000172:deficiency*; D010641:Phenotype; D044465:White People
chemical_list: D010430:Pentosyltransferases; D000228:Adenine Phosphoribosyltransferase