title: Identification of a new point mutation in the human xanthine dehydrogenase gene responsible for a case of classical type I xanthinuria.
abstract: A 60-year-old Japanese man was diagnosed as having hypouricemia at an annual health check-up. The routine laboratory data was not remarkable except that the patient's hypouricemia and plasma levels of xanthine and hypoxanthine were much higher than those of normal subjects. Furthermore, the patient's daily urinary excretion of xanthine and hypoxanthine was markedly increased compared with reference values. The xanthine dehyrogenase activity of the duodenal mucosa was below the limits of detection. Nevertheless, allopurinol was metabolized to oxypurinol in vivo. Based on these findings, a subtype of classical xanthinuria (type I) was diagnosed. The xanthine dehyrogenase protein was detected by Western blotting analysis. Sequencing of the cDNA of the xanthine dehyrogenase obtained from the duodenal mucosa revealed that 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 previously reported in patients with classical xanthinuria type I.
authors.affiliation: Department of Internal Medicine, Harima Hospital of Ishikawajima-harima Heavy Industries, Health Insurance Society, Aioi, Hyogo, Japan. AS1011@ihi.co.jp
authors.forename: N
authors.initials: N
authors.lastname: Sakamoto
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Moriwaki
authors.forename: T
authors.initials: T
authors.lastname: Teranishi
authors.forename: M
authors.initials: M
authors.lastname: Toyoda
authors.forename: Y
authors.initials: Y
authors.lastname: Onishi
authors.forename: S
authors.initials: S
authors.lastname: Kuroda
authors.forename: K
authors.initials: K
authors.lastname: Sakaguchi
authors.forename: T
authors.initials: T
authors.lastname: Fujisawa
authors.forename: M
authors.initials: M
authors.lastname: Maeda
authors.forename: T
authors.initials: T
authors.lastname: Hada
mesh_terms: D000493:Allopurinol / Q000008:administration & dosage / Q000652:urine; D006801:Humans; D019271:Hypoxanthine / Q000097:blood / Q000652:urine*; D008297:Male; D008875:Middle Aged; D010117:Oxypurinol / Q000652:urine; D017354:Point Mutation; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology / Q000652:urine; D017422:Sequence Analysis, DNA; D019820:Xanthine / Q000097:blood / Q000652:urine*; D014968:Xanthine Dehydrogenase / Q000235:genetics* / Q000378:metabolism
chemical_list: D019820:Xanthine; D019271:Hypoxanthine; D000493:Allopurinol; D014968:Xanthine Dehydrogenase; D010117:Oxypurinol