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

• Published in: Human genetics Vol. 108; no. 4; pp. 279 - 283
• Main Authors: SAKAMOTO, Norikazu, YAMAMOTO, Tetsuya, HADA, Toshikazu, MORIWAKI, Yuji, TERANISHI, Tetsuya, TOYODA, Masanori, ONISHI, Yutaka, KURODA, Shoji, SAKAGUCHI, Kazuhiko, FUJISAWA, Takashi, MAEDA, Mitsuo
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01-04-2001; Berlin; New York, NY
• Subjects: Allopurinol - administration & dosage; Allopurinol - urine; Biological and medical sciences; Humans; Hypoxanthine - blood; Hypoxanthine - urine; Male; Medical sciences; Metabolic diseases; Middle Aged; Other metabolic disorders; Oxypurinol - urine; Point Mutation; Purine-Pyrimidine Metabolism, Inborn Errors - enzymology; Purine-Pyrimidine Metabolism, Inborn Errors - genetics; Purine-Pyrimidine Metabolism, Inborn Errors - physiopathology; Purine-Pyrimidine Metabolism, Inborn Errors - urine; Purines and pyrimidines (gout, hyperuricemia...); Sequence Analysis, DNA; Xanthine - blood; Xanthine - urine; Xanthine Dehydrogenase - genetics; Xanthine Dehydrogenase - metabolism; Kidney disease; Human; Urinary system disease; Nucleotide sequence; Enzyme; Tubulopathy; Xanthine dehydrogenase; Xanthinuria; Metabolic diseases; Enzymopathy; Complementary DNA; Gene; Point mutation; Purine; Oxidoreductases; Aminoacid disorder; Aminoaciduria
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s004390100477

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.