XDH gene mutation is the underlying cause of classical xanthinuria: A second report

Background. Classical xanthinuria is a rare autosomal recessive disorder ch aracterized by excessive excretion of xanthine in urine. Type I disease res ults from the isolated deficiency of xanthine dehydrogenase (XDH), and type II results from dual deficiency of XDH and aldehyde oxidase. The XDH gene has been cloned and localized to chromosome 2p22-23. The aim of this study was to characterize the molecular basis of classical xanthinuria in an Iran ian-Jewish family. Methods. The apparently unrelated parents originated from a community in wh ich consanguineous marriages are common. Subtyping xanthinuria was attempte d by homozygosity mapping using microsatellite markers D2S352, D2S367, and D2S2374 in the vicinity of the XDH gene. Mutation detection was accomplishe d by PCR-SSCP screening of all 36 exons and exon-intron junctions of the XD H gene, followed by direct sequencing and confirmation of sequence alterati on by restriction analysis. Results. The index case was homozygous for all three microsatellite markers analyzed. The expected frequency of this genotype in a control population was 0.0002. These results suggested that xanthinuria in the patient is link ed to the XDH gene. Consequently, a 1658insC mutation in exon 16 of the XDH gene was identified. The 1658insC mutation was not detected in 65 control DNA samples. Conclusion. A molecular approach to the diagnosis of classical xanthinuria type I in a female patient with profound hypouricemia is described. Linkage of xanthinuria to the XDH locus was demonstrated by homozygosity mapping, and a 1658insC mutation, predicting a truncated inactive XDH protein, was i dentified. These results reinforce the notion that mutations in the XDH gen e are the underlying cause of classical xanthinuria type I.