Levartovsky D, Lagziel A, Sperling O, Liberman U, Yaron M, Hosoya T, Ichida K, Peretz H
Tel Aviv Sourasky Medical Center and Rabin Medical Center, Tel Aviv University, Tel Aviv, Israel.
Kidney Int. 2000 Jun;57(6):2215-20. doi: 10.1046/j.1523-1755.2000.00082.x.
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 2p22-23. The aim of this study was to characterize the molecular basis of classical xanthinuria in an Iranian-Jewish family.
The apparently unrelated parents originated from a community in which consanguineous marriages are common. Subtyping xanthinuria was attempted by homozygosity mapping using microsatellite markers D2S352, D2S367, and D2S2374 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 1658insC mutation in exon 16 of the XDH gene was identified. The 1658insC 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 1658insC 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.
经典型黄嘌呤尿症是一种罕见的常染色体隐性疾病，其特征是尿液中黄嘌呤排泄过多。I型疾病是由于黄嘌呤脱氢酶（XDH）单独缺乏所致，II型是由于XDH和醛氧化酶双重缺乏所致。XDH基因已被克隆并定位于2号染色体p22 - 23区域。本研究的目的是确定一个伊朗犹太人家族中经典型黄嘌呤尿症的分子基础。
表面上无血缘关系的父母来自一个近亲结婚很常见的社区。尝试通过使用XDH基因附近的微卫星标记D2S352、D2S367和D2S2374进行纯合性定位来对黄嘌呤尿症进行亚型分类。通过对XDH基因的所有36个外显子和外显子 - 内含子连接区进行PCR - SSCP筛选来完成突变检测，随后进行直接测序，并通过限制性分析确认序列改变。
索引病例对所分析的所有三个微卫星标记均为纯合子。该基因型在对照人群中的预期频率为0.0002。这些结果表明患者的黄嘌呤尿症与XDH基因相关。因此，在XDH基因的第16外显子中鉴定出一个1658insC突变。在65份对照DNA样本中未检测到1658insC突变。
描述了一种对一名患有严重低尿酸血症的女性患者进行经典I型黄嘌呤尿症诊断的分子方法。通过纯合性定位证明了黄嘌呤尿症与XDH基因座的连锁关系，并鉴定出一个1658insC突变，该突变预测会产生截短的无活性XDH蛋白。这些结果强化了XDH基因突变是经典I型黄嘌呤尿症根本原因的观点。
