Ichida K, Amaya Y, Kamatani N, Nishino T, Hosoya T, Sakai O
Second Department of Medicine, The Jikei University School of Medicine, Tokyo 105.
J Clin Invest. 1997 May 15;99(10):2391-7. doi: 10.1172/JCI119421.
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.
遗传性黄嘌呤尿症分为三类。经典的I型黄嘌呤尿症仅缺乏黄嘌呤脱氢酶活性，而II型和钼辅因子缺乏症还缺乏一种或两种其他酶活性。在本研究中，我们检查了四名患有经典黄嘌呤尿症的个体，以在分子水平上发现酶缺乏的原因。一名受试者在核苷酸682处发生了C到T的碱基替换，这应该导致密码子228处的CGA（精氨酸）到TGA（终止）无义替换。该受试者的十二指肠粘膜没有黄嘌呤脱氢酶蛋白，而mRNA水平没有降低。两名患有I型黄嘌呤尿症的同胞受试者在该突变方面是纯合子，而另一名受试者被发现以杂合状态含有相同的突变。最后一名同样患有I型黄嘌呤尿症的受试者在cDNA的核苷酸2567处缺失了C，这应该从核苷酸2783产生一个终止密码子。该受试者在该突变方面是纯合子，并且该受试者十二指肠粘膜中的mRNA水平没有降低。因此，在三名I型黄嘌呤尿症受试者中，主要的遗传缺陷被证实存在于黄嘌呤脱氢酶基因中。
