Novel mutations in xanthine dehydrogenase/oxidase cause severe hypouricemia: biochemical and molecular genetic analysis in two Czech families with xanthinuria type I
Language English Country Netherlands Media print-electronic
Document type Case Reports, Journal Article, Research Support, Non-U.S. Gov't
PubMed
21963464
DOI
10.1016/j.cca.2011.08.038
PII: S0009-8981(11)00495-5
Knihovny.cz E-resources
- MeSH
- DNA Primers MeSH
- Adult MeSH
- Electrophoresis, Polyacrylamide Gel MeSH
- Haplotypes MeSH
- Uric Acid blood MeSH
- Humans MeSH
- Microsatellite Repeats MeSH
- Mutation * MeSH
- Base Sequence MeSH
- Blotting, Western MeSH
- Xanthine urine MeSH
- Xanthine Dehydrogenase genetics MeSH
- Xanthine Oxidase genetics MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
- Names of Substances
- DNA Primers MeSH
- Uric Acid MeSH
- Xanthine MeSH
- Xanthine Dehydrogenase MeSH
- Xanthine Oxidase MeSH
BACKGROUND: The article describes the clinical, biochemical, enzymological and molecular genetics findings in two patients from two families with xanthinuria type I. METHODS: Biochemical analysis using high performance liquid chromatography, allopurinol loading test and analysis of xanthine oxidase activity in plasma and of uromodulin excretion in urine were performed. Sequencing analysis of the xanthine dehydrogenase gene and the haplotype and statistical analyses of consanguinity were performed. RESULTS: Probands showed extremely low concentrations of uric acid, on seven occasions under the limit of detection. The concentration of uric acid in 38-year-old female was 15 μmol/L in serum and 0.04 mmol/L in urine. Excretion of xanthine in urine was 170 mmol/mol creatinine. The concentration of uric acid in 25-year-old male was 0.03 mmol/L in urine. Excretion of xanthine in urine was 141 mmol/mol creatinine. The allopurinol loading test confirmed xanthinuria type I. The xanthine oxidase activities in patients were 0 and 0.4 pmol/h/mL of plasma. We found three nonsense changes: p.P214QfsX4 and unpublished p.R825X and p.R881X. CONCLUSIONS: We found two nonconsanguineous compound heterozygotes with xanthinuria type I caused by three nonsense changes. The methods used did not confirm consanguinity in the probands, thus there might be an unconfirmed biological relationship or mutational hotspot.
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