Identification of a new point mutation in the human xanthine dehydrogenasegene responsible for a case of classical type I xanthinuria

Citation
N. Sakamoto et al., Identification of a new point mutation in the human xanthine dehydrogenasegene responsible for a case of classical type I xanthinuria, HUM GENET, 108(4), 2001, pp. 279-283
Citations number
17
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
HUMAN GENETICS
ISSN journal
0340-6717 → ACNP
Volume
108
Issue
4
Year of publication
2001
Pages
279 - 283
Database
ISI
SICI code
0340-6717(200104)108:4<279:IOANPM>2.0.ZU;2-K
Abstract
A 60-year-old Japanese man was diagnosed as having hypouricemia at an annua l health check-up. The routine laboratory data was not remarkable except th at the patient's hypouricemia and plasma levels of xanthine and hypoxanthin e were much higher than those of normal subjects. Furthermore, the patient' s daily urinary excretion of xanthine and hypoxanthine was markedly increas ed compared with reference values. The xanthine dehyrogenase activity of th e duodenal mucosa was below the limits of detection. Nevertheless, allopuri nol was metabolized to oxypurinol in vivo. Based on these findings, a subty pe of classical xanthinuria (type I) was diagnosed. The xanthine dehyrogena se protein was detected by Western blotting analysis. Sequencing of the cDN A of the xanthine dehyrogenase obtained from the duodenal mucosa revealed t hat a point mutation of C to T had occurred in nucleotide 445. This changed codon 149 from CGC (Arg) to TGC (Cys), a finding that has not been previou sly reported in patients with classical xanthinuria type I.