title: Identification of a new point mutation in the human molybdenum cofactor sulferase gene that is responsible for xanthinuria type II.
abstract: A 43-year-old xanthinuric female was referred to our department because of hypouricemia. Routine laboratory data showed hypouricemia, a high level of plasma oxypurines, decreased urinary uric acid excretion, and increased urinary oxypurine excretion, with xanthine dehydrogenase activity in the duodenal mucosa below the limits of detection. In addition, allopurinol was not metabolized. From these findings, the patient was diagnosed with xanthinuria type II. To investigate the properties of xanthine dehydrogenase/xanthine oxidase (XDH/XO) deficiency, a cDNA sequence encoding XDH/XO, aldehyde oxidase (AO), and molybdenum cofactor sulferase (MCS), as well as immunoblotting analysis for XDH/XO protein, obtained from duodenal mucosa samples were performed. The XDH/XO cDNA and AO cDNA sequences of the xanthinuric patient were consistent with previously reported ones, whereas the MCS cDNA sequence revealed a point mutation of G to C in nucleotide 466, which changed codon 156 from GCC (Ala) to CCC (Pro). In addition, the MCS genomic DNA sequence including the site of the mutation revealed the same, suggesting that the xanthinuric patient was homozygous for this mutation. Such findings have not been previously reported for patients with xanthinuria type II.
authors: Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
authors: Tetsuya
authors: T
authors: Yamamoto
authors: Yuji
authors: Y
authors: Moriwaki
authors: Sumio
authors: S
authors: Takahashi
authors: Zenta
authors: Z
authors: Tsutsumi
authors: Ka
authors: K
authors: Tuneyoshi
authors: Kiyoshi
authors: K
authors: Matsui
authors: Jidong
authors: J
authors: Cheng
authors: Toshikazu
authors: T
authors: Hada
mesh_terms: D000328:Adult; D042931:Aldehyde Oxidase / Q000378:metabolism; D000493:Allopurinol; D000963:Antimetabolites; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D004386:Duodenum / Q000201:enzymology; D005260:Female; D006801:Humans; D019271:Hypoxanthine / Q000652:urine; D015151:Immunoblotting; D007413:Intestinal Mucosa / Q000201:enzymology; D017354:Point Mutation / Q000235:genetics / Q000502:physiology*; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000235:genetics* / Q000652:urine; D013466:Sulfurtransferases / Q000235:genetics*; D014527:Uric Acid / Q000652:urine; D014968:Xanthine Dehydrogenase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism; D014970:Xanthines / Q000652:urine*
chemical_list: D000963:Antimetabolites; D017931:DNA Primers; D018076:DNA, Complementary; D014970:Xanthines; D014527:Uric Acid; D019271:Hypoxanthine; D000493:Allopurinol; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D042931:Aldehyde Oxidase; C425823:MOCOS protein, human; D013466:Sulfurtransferases