title: Hypoxanthine guanine phosphoribosyltransferase deficiency: nucleotide substitution causing Lesch-Nyhan syndrome identified for the first time among Japanese.
abstract: A previously undescribed nucleotide substitution at codon 51 (CGA to TGA) has been identified using the polymerase chain reaction technique in hypoxanthine guanine phosphoribosyltransferase (HPRT) cDNA; this is the first molecular evidence for a point mutation in a Japanese patient with Lesch-Nyhan syndrome. The present mutation is the 19th nucleotide substitution identified as a germ-line mutation at this locus and the second mutation generating a stop codon. The position of the nucleotide substitution is exactly the same as a previously described mutation HPRTToronto, indicating for the first time that nucleotide substitutions at the same position in the sequence of HPRT can generate different mutant alleles, one causing a partial deficiency and the other a complete deficiency. Although the type of nucleotide substitution is different between the two cases, a single base position has twice become the target of a mutation. However, the calculation of the probability of finding substitution mutations at the same base position in the coding region of hprt indicates that there is no evidence for the presence of a hot spot for substitution mutations in the human hprt germ line.
authors.affiliation: Second Department of Internal Medicine, University of Teikyo, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Fujimori
authors.forename: N
authors.initials: N
authors.lastname: Kamatani
authors.forename: Y
authors.initials: Y
authors.lastname: Nishida
authors.forename: N
authors.initials: N
authors.lastname: Ogasawara
authors.forename: I
authors.initials: I
authors.lastname: Akaoka
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D003062:Codon; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D007564:Japan; D007926:Lesch-Nyhan Syndrome / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction
chemical_list: D003062:Codon; D007041:Hypoxanthine Phosphoribosyltransferase