Novel Uromodulin Mutation in Familial Juvenile Hyperuricemic Nephropathy
Novel Uromodulin Mutation in Familial Juvenile Hyperuricemic Nephropathy
复制标题
家族性青少年高尿酸血症肾病中的新型尿调节蛋白突变
DOI：
10.1159/000339752
复制
发表时间：
2012-01-01
影响因子：
4.2
通讯作者：
Chen, Wei
中科院分区：
文献类型：
--
作者：
Wei, Xin;Xu, Ricong;Chen, Wei
背景：家族性青少年高尿酸血症肾病（FJHN）是一种常染色体显性遗传疾病，其特征是早发高尿酸血症、肾脏尿酸盐排泄分数减少和进行性间质性肾病。编码尿调节素/Tamm-Horsfall（一种糖基磷脂酰肌醇（GPI）锚定蛋白）的尿调节素（UMOD）基因突变会导致这种疾病。方法：描述了一个有 13 名 FJHN 患者的中国家庭。收集了 7 名受影响成员（该家庭中所有活着的患者）和 15 名未受影响成员的临床资料、血液和尿液样本。通过聚合酶链式反应和直接测序进行UMOD基因的突变分析。通过酶联免疫吸附测定试剂盒检查来自该家庭受影响或未受影响成员以及健康对照的尿液尿调节素。免疫荧光显示肾组织中尿调节素的表达。结果：在该 FJHN 家族的受影响个体中，发现了尿调节素 GPI 锚定信号片段内的新突变 (p.T605G)。在估计肾小球滤过率<60 ml/min/1.73 m2的受影响患者中，肾组织中尿调节素的表达显着增加，尿调节素的尿液排泄显着减少。结论：本研究报告了中国汉族人群中 UMOD 外显子 9 的新突变，位于尿调节素的 GPI 锚信号片段内。由于 GPI 锚与蛋白质的释放或分泌有关，我们的发现可能为 FJHN 中尿调节素尿排泄减少的潜在机制提供进一步的证据。
Background: Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal dominant disorder characterized by early onset of hyperuricemia, decreased fractional renal urate excretion and progressive interstitial nephropathy. Mutations in the uromodulin (UMOD) gene encoding uromodulin/Tamm-Horsfall, a glycosylphosphatidylinositol (GPI)-anchored protein, cause this disease. Methods: One Chinese family with 13 FJHN-affected individuals is described. Clinical data, blood and urine samples of 7 affected members (all alive patients in this family) and 15 unaffected members were collected. Mutation analysis of the UMOD gene was performed by polymerase chain reaction and direct sequencing. Urinary uromodulin from affected or unaffected members of this family and healthy controls was examined by enzyme-linked immunosorbent assay kit. Expression of uromodulin in renal tissue was shown with immunofluorescence. Results: A novel mutation (p.T605G) within the uromodulin GPI anchor signal segment was identified in the affected individuals of this FJHN family. There was a markedly increased expression of uromodulin in renal tissue and significantly decreased urinary excretion of uromodulin in affected patients with an estimated glomerular filtration rate <60 ml/min/1.73 m2. Conclusions: The present study reported a novel mutation in exon 9 of UMOD in the Chinese Han population, within the GPI anchor signal segment of uromodulin. Since the GPI anchor is linked with the release or secretion of proteins, our finding may provide further evidence for the underlying mechanism of decreased urinary excretion of uromodulin in FJHN.