目的探讨尿调蛋白(又称Tamm Horsfall 蛋白)基因突变检测在家族性高尿酸血症和/或家族性肾小管间质肾病诊断中意义。方法对诊断为家族性高尿酸血症和/或家族性小管间质肾病的20 例患者，收集家系临床资料，并进行尿调蛋白基因突变筛查。同时收集肾脏病理活检活检诊为慢性肾小管间质肾病且家族史阴性的患者30 例，整理临床资料。结果20 例患者中发现5 例患者存在尿调蛋白基因不同位点突变，突变检出率为25%，其中2 例已报道,3 例为国内外尚未报道的新突变。新突变中2 个为错义突变(c.1153C/T,p.Arg385Trp；c.197T/C,p.Leu66Pro)，分别位于3 号和5 号外显子上；另一个为3 号外显子上导致移码突变和终止密码提前的单碱基缺失(272del C)。将以上20 例患者分成尿调蛋白突变组、尿调蛋白未突变组，与30 例家族史阴性的慢性小管间质肾病组相比较，发现家族史阳性的两组患者其年龄均显著低于家族史阴性组(P＜0.01,P＜0.01)，而血尿酸水平则均明显高于家族史阴性组(P＜0.01，P =0.030)，但以上指标在家族史阳性的尿调蛋白未突变组与尿调蛋白突变组之间无显著性差异。结论家族性高尿酸血症和/或家族性肾小管间质肾病，进行尿调蛋白的基因突变检测有一定的诊断意义，而对于尿调蛋白突变阴性的患者，需进一步筛查其他基因。在中国人群发现了3 个新的尿调蛋白基因致病突变，扩展了尿调蛋白相关肾病的基因突变谱。

Objectives To explore the clinical significance of uromodulin (Tamm Horsfall protein) gene mutations in the diagnosis of familial hyperuricemia and/or familial renal tubular interstitial nephropathy. Methods Mutations in the Tamm-Horsfall protein gene were screened by PCR and sequencing in the 20 patients clinically diagnosed with familial hyperuricemia or familial renal tubular interstitial nephropathy. Results We found 5 patients with mutations in the Tamm Horsfall protein gene. Two of them have been reported by us, and 3 of them carried two new missense mutations (c.1153C>T, p.Arg385Trp; c.197T>C, p.Leu66Pro) and one new deletion mutation (272delC) that have not been reported previously. Conclusion We found 3 new mutations in Tamm Horsfall protein gene by mutation screening in Chinese patients, which extends the mutation spectrum of Tamm Horsfall protein gene.