Puig J G, Prior C, Martínez-Ara J, Torres R J
Division of Internal Medicine, Hospital Universitario La Paz, Madrid, Spain.
Nucleosides Nucleotides Nucleic Acids. 2006;25(9-11):1295-300. doi: 10.1080/15257770600894766.
Since 1993 we have studied 5 Spanish families with familial nephropathy associated with hyperuricemia (FJHN). Among these families, 24 patients have been identified. All patients had some combination of hyperuricemia, gout, renal insufficiency, arterial hypertension, and reduced kidney size. The clinical presentation in the different families and in the members of the same family was heterogeneous. Allopurinol treatment did not appear to influence renal disease. From a clinical perspective, this syndrome is a distinctive interstitial nephropathy, inherited as an autosomal dominant trait, that progresses to renal failure and is not halted nor prevented by allopurinol therapy. In 2003, genetic linkage analysis in 3 of the 5 families showed linkage of FJHN to 16p 11.2. One family was not analyzed and one family did not show linkage to this region confirming the genetic heterogeneity of this syndrome. A mutation in UMOD gene was found in these 3 families as the cause of the FJHN. The mutations cluster in exon 4 and exon 5 and were point mutation that results in an amino acid change in the uromodulin or Tamm Horsfall protein. This fact allowed in 2004, the presymptomatic genetic diagnosis of an 8-years-old boy belonging to one of these 3 Spanish families. We conclude that in families with a history of renal failure and/or gout in which FJHN is suspected, UMOD mutation screening may enable a definite diagnosis. When a mutation is found, family members can be tested for a UMOD mutation and pre-symptomatic diagnosis may allow counseling to prevent or halt the progression to renal insufficiency.
自1993年以来，我们对5个患有与高尿酸血症相关的家族性肾病（FJHN）的西班牙家庭进行了研究。在这些家庭中，已确定了24名患者。所有患者都有高尿酸血症、痛风、肾功能不全、动脉高血压和肾脏缩小的某种组合。不同家庭以及同一家族成员的临床表现是异质性的。别嘌醇治疗似乎并未影响肾脏疾病。从临床角度来看，这种综合征是一种独特的间质性肾病，以常染色体显性性状遗传，会进展为肾衰竭，且别嘌醇治疗无法阻止或预防其发展。2003年，对5个家庭中的3个进行的基因连锁分析显示，FJHN与16p 11.2连锁。有一个家庭未进行分析，另一个家庭未显示与该区域连锁，这证实了该综合征的基因异质性。在这3个家庭中发现UMOD基因突变是FJHN的病因。这些突变集中在外显子4和外显子5，是导致尿调节蛋白或Tamm Horsfall蛋白氨基酸改变的点突变。这一事实使得在2004年能够对来自这3个西班牙家庭之一的一名8岁男孩进行症状前基因诊断。我们得出结论，在怀疑患有FJHN且有肾衰竭和/或痛风病史的家庭中，UMOD突变筛查可能有助于明确诊断。当发现突变时，可以对家庭成员进行UMOD突变检测，症状前诊断可能有助于提供咨询，以预防或阻止进展为肾功能不全。
