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

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Classical xanthinuria is a rare autosomal recessive disorder characterized by excessive excretion of xanthine in urine . Type I disease results 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 2 p 22 -23 . The aim of this study was to characterize the molecular basis of classical xanthinuria in an Iranian -Jewish family .T he apparently unrelated parents originated from a community in which consanguineous marriages are common . Subtyping xanthinuria was attempted by homozygosity mapping using microsatellite markers D 2 S 352 , D 2 S 367 , and D 2 S 2374 in the vicinity of the XDH gene . Mutation detection was accomplished by PCR-SSCP screening of all 36 exons and exon-intron junctions of the XDH gene , followed by direct sequencing and confirmation of sequence alteration by restriction analysis .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 linked to the XDH gene . Consequently , a 1658 insC mutation in exon 16 of the XDH gene was identified . The 1658 insC mutation was not detected in 65 control DNA samples .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 1658 insC mutation , predicting a truncated inactive XDH protein , was identified . These results reinforce the notion that mutations in the XDH gene are the underlying cause of classical xanthinuria type I .