Scheinman S J, Cox J P, Lloyd S E, Pearce S H, Salenger P V, Hoopes R R, Bushinsky D A, Wrong O, Asplin J R, Langman C B, Norden A G, Thakker R V
Department of Medicine, SUNY Health Science Center, Syracuse, New York 13210, USA.
Kidney Int. 2000 Jan;57(1):232-9. doi: 10.1046/j.1523-1755.2000.00774.x.
Isolated hypercalciuria with mutation in CLCN5: Relevance to idiopathic hypercalciuria.
Idiopathic hypercalciuria (IH) is the most common risk factor for kidney stones and often has a genetic component. Dent's disease (X-linked nephrolithiasis) is associated with mutations in the CLCN5 chloride channel gene, and low molecular weight (LMW) proteinuria was universally observed in affected males. We sought to identify mutations in CLCN5 or abnormalities in LMW protein excretion in a large group of patients with IH and in a rat model of genetic hypercalciuria.
One hundred and seven patients with IH (82 adults and 25 children) and one asymptomatic hypercalciuric man with a known inactivating mutation in CLCN5 were studied. Secondary causes of hypercalciuria were excluded in all. The excretion of retinol-binding protein and beta2-microglobulin was measured by immunoassay in 101 patients with IH. Mutation analysis of the CLCN5 gene was performed in 32 patients with IH and in the genetic hypercalciuric stone-forming (GHS) rat strain.
LMW protein excretion was normal in 92 patients with IH, and only slight abnormalities were found in the other nine, none of whom had a mutation in CLCN5. One 27-year-old man who had a CLCN5 mutation was found to have isolated hypercalciuria without LMW proteinuria, renal failure, or other evidence of renal disease. Mutation analysis was normal in 32 patients with IH. The CLCN5 sequence was normal in the GHS rat.
Inactivation of CLCN5 can be found in the setting of hypercalciuria without other features of X-linked nephrolithiasis. However, mutations in CLCN5 do not represent a common cause of IH.
CLCN5基因突变导致的孤立性高钙尿症：与特发性高钙尿症的相关性
特发性高钙尿症（IH）是肾结石最常见的危险因素，且常具有遗传成分。丹特病（X连锁肾结石病）与CLCN5氯离子通道基因突变相关，在受影响的男性中普遍观察到低分子量（LMW）蛋白尿。我们试图在一大组IH患者和遗传性高钙尿症大鼠模型中鉴定CLCN5基因突变或LMW蛋白排泄异常情况。
研究了107例IH患者（82例成人和25例儿童）以及1例已知CLCN5基因失活突变的无症状高钙尿症男性。排除了所有高钙尿症的继发原因。对101例IH患者采用免疫分析法测定视黄醇结合蛋白和β2微球蛋白的排泄量。对32例IH患者和遗传性高钙尿症结石形成（GHS）大鼠品系进行CLCN5基因突变分析。
92例IH患者的LMW蛋白排泄正常，其他9例仅发现轻微异常，且均无CLCN5基因突变。发现1例27岁男性有CLCN5基因突变，其表现为孤立性高钙尿症，无LMW蛋白尿、肾衰竭或其他肾脏疾病证据。3位IH患者的突变分析结果正常。GHS大鼠的CLCN5序列正常。
在无X连锁肾结石病其他特征的高钙尿症患者中可发现CLCN5基因失活。然而，CLCN5基因突变并非IH的常见病因。
