Identification of two mutations in human xanthine dehydrogenase gene responsible for classical type I xanthinuria.

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Hereditary xanthinuria is classified into three categories . Classical xanthinuria type I lacks only xanthine dehydrogenase activity , while type II and molybdenum cofactor deficiency also lack one or two additional enzyme activities . In the present study , we examined four individuals with classical xanthinuria to discover the cause of the enzyme deficiency at the molecular level . One subject had a C to T base substitution at nucleotide 682 that should cause a CGA (Arg ) to TGA (Ter ) nonsense substitution at codon 228 . The duodenal mucosa from the subject had no xanthine dehydrogenase protein while the mRNA level was not reduced . The two subjects who were siblings with type I xanthinuria were homozygous concerning this mutation , while another subject was found to contain the same mutation in a heterozygous state . The last subject who was also with type I xanthinuria had a deletion of C at nucleotide 2567 in cDNA that should generate a termination codon from nucleotide 2783 . This subject was homozygous for the mutation and the level of mRNA in the duodenal mucosa from the subject was not reduced . Thus , in three subjects with type I xanthinuria , the primary genetic defects were confirmed to be in the xanthine dehydrogenase gene .