title: Molecular analysis of HPRT deficiencies: an update of the spectrum of Asian mutations with novel mutations.
abstract: Inherited mutations of a purine salvage enzyme, hypoxanthine guanine phosphoribosyltransferase (HPRT, EC 2.4.2.8), give rise to Lesch-Nyhan syndrome or HPRT-related gout. We have identified a number of HPRT mutations in Asian patients manifesting different clinical phenotypes, by analyzing all nine exons of the HPRT gene (HPRT1) from genomic DNA and reverse-transcribed mRNA using the PCR technique coupled with direct sequencing. In this study, we update the spectrum of mutations with nine novel mutations. Two missense mutations (T124P and D185G) were detected in patients with HRH (HPRT-related hyperuricemia). In a patient having a severe partial deficiency of HPRT with neurological dysfunction (HRND: HPRT-related neurological dysfunction), a single nucleotide substitution (27+5G > A) causing a splicing error was found in intron 1. The mutation resulted in a remarkably decreased level of normal mRNA, and production of an abnormal mRNA with a 49-bp insert at the 5'-end of intron 1, which caused the frame-shift of an amino acid codon (10fs27X). In six typical Lesch-Nyhan families, we found two 3-bp deletions responsible for single amino acid deletions (V8del and Y28del), two 1-bp deletions (440delA and 635delG) generating a frame-shift, an insertion of two amino acids (159insKV), and a 4,131-bp deletion from introns 4 to 6 resulting in two types of abnormal mRNA. Including these nine mutations, 42 HPRT1 mutations have been identified among 47 Asian families with deficiency of HPRT.
authors.affiliation: Department of Genetics, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi 480-0392, Japan. yasyam@inst-hsc.jp
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Yamada
authors.forename: Noriko
authors.initials: N
authors.lastname: Nomura
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Yamada
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Wakamatsu
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics*; D001208:Asia; D001483:Base Sequence; D005260:Female; D006073:Gout / Q000235:genetics*; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency* / Q000235:genetics; D007926:Lesch-Nyhan Syndrome / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D017384:Sequence Deletion
chemical_list: D007041:Hypoxanthine Phosphoribosyltransferase