title: Molecular analysis of two enzyme genes, HPRT1 and PRPS1, causing X-linked inborn errors of purine metabolism.
abstract: Inherited mutation of hypoxanthine guanine phosphoribosyltransferase (HPRT) gives rise to Lesch-Nyhan syndrome or HPRT-related gout. On the other hand, PRPS1 mutations cause PRPP synthetase superactivity associated with hyperuricemia and gout, sometimes including neurodevelopmental abnormalities. We have identified two mutations in two Lesch-Nyhan families after our last report. One of them, a new single nucleotide substitution (130G>T) resulting in a missense mutation D44Y was detected in exon 2 of HPRT1. RT-PCR amplification showed not only a cDNA fragment with normal size, but also a small amount of shorter fragment skipping exons 2 and 3. The other missense mutation F74L (222C > A) was detected in a Japanese patient but has been reported previously in European families. In four hyperuricemic patients with mild neurological abnormality, no mutations responsible for partial HPRT deficiency were identified in HPRT1. In these four patients, we also performed molecular analysis of PRPS1, but no mutations in PRPP synthetase were found.
authors.affiliation: Department of Genetics, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan. yasyam@inst-hsc.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: N
authors.initials: N
authors.lastname: Nomura
authors.forename: A
authors.initials: A
authors.lastname: Yamano
authors.forename: R
authors.initials: R
authors.lastname: Kimura
authors.forename: S
authors.initials: S
authors.lastname: Tomida
authors.forename: M
authors.initials: M
authors.lastname: Naiki
authors.forename: N
authors.initials: N
authors.lastname: Wakamatsu
mesh_terms: D004252:DNA Mutational Analysis; D040181:Genetic Diseases, X-Linked / Q000201:enzymology; D020022:Genetic Predisposition to Disease; D006801:Humans; D033461:Hyperuricemia / Q000209:etiology / Q000235:genetics; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D007926:Lesch-Nyhan Syndrome / Q000209:etiology / Q000235:genetics; D011687:Purines / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012268:Ribose-Phosphate Pyrophosphokinase / Q000235:genetics / Q000378:metabolism
chemical_list: D011687:Purines; D007041:Hypoxanthine Phosphoribosyltransferase; C510474:PRPS1 protein, human; D012268:Ribose-Phosphate Pyrophosphokinase; C030985:purine