Objective To summarize the clinical features and genetic analysis results of 10 children with Dent disease.Methods The clinical data and gene test results of 10 boys aged from 8 months to 12 years with Dent disease diagnosed in Children's Hospital of Nanjing Medical University from January 2014 to July 2017 were analyzed retrospectively.Results All patients had insidious onset,5 cases were found to have proteinuria on routine urine examination after hospitalization duo to other diseases,4 cases were admitted to hospital because increased foams in the urine,and 1 case was found to have proteinuria on health checkup.All cases presented with low molecular weight proteinuria,urine protein electrophoresis showed that the proportion of low molecular weight protein was greater than 50％,7 cases had nephrotic-range proteinuria,but none had hypoproteinemia.Six cases had hypercalciuria,3 cases had nephrocalcinosis,1 case had nephrolithiasis,2 cases had glomerular microscopic hematuria,in 1 case urine glucose wa weakly positive but blood glucose was normal.All patients had normal renal function,normal serum calcium,no hypophosphoremia and none had rickets.Genetic analysis results showed that 7 patients with variants in the CLCN5 gene,including 2 nonsense variants (p.R637X,p.Y143X),3 missense variants (p.A540D,p.G135E,p.G703V),1 deletion variant (exons 9,10,11,12,13,1 missing),and 1 frameshift variant (p.T260Tfs* 10).Three cases had missense variants of OCRL gene (p.1274T,p.I37 1T,p.F399S).Except for p.R637X and p.I274T,the other 8 cases had newly discovered variants.Five patients underwent a renal biopsy,the biopsy revealed focal global glomerulosclerosis in 3 patients,mild mesangial proliferative glomerulonephritis in 1 patient and renal minimal change in 1 patient.Mild focal tubular atrophy and interstitial fibrosis were noted in three cases.Mild segmental foot process effacement was noted under electron microscope in all five cases.Conclusions All the children with Dent disease had insidious onset,low molecular weight proteinuria is the main clinical manifestation,most cases presented with nephrotic-range proteinuria,but there was no hypoalbuminemia,some cases were not associated with hypercalciuria.The pathogenic genes in most cases were CLCN5 and a few were OCRL.The types of genetic variation include missense variant,nonsense variant,deletion variant and frameshift variant.Although Dent disease is a renal tubular disease,renal biopsy suggests that most cases are associated with glomerular lesions.%目的 总结10例Dent病患儿的临床特征及基因检测结果.方法 回顾性分析2014年1月至2017年7月在南京医科大学附属儿童医院肾脏科住院确诊的10例Dent病患儿的临床资料及基因检测结果.结果 10例患儿均为男性,起病年龄8月龄～ 12岁不等.患儿起病隐匿,5例因其他疾病住院行尿常规检查发现蛋白尿,4例因发现尿中泡沫增多就诊,1例体检发现蛋白尿.临床均表现为低相对分子质量(简称低分子量)蛋白尿,尿蛋白电泳提示低分子量蛋白比例大于50％,其中7例患儿呈肾病水平蛋白尿,均无低蛋白血症.6例伴高钙尿症,3例伴肾钙质沉着,1例伴肾结石,2例伴有镜下肾小球源性血尿,1例尿糖弱阳性但血糖正常.所有病例肾功能正常,血钙正常,无低磷血症,临床均无佝偻病表现.基因检测结果显示7例患儿为CLCN5基因变异,包括2个无义变异(分别为p.R637X、p.Y143X)、3个错义变异(分别为p.A540D、p.G135E、p.G703V)、1个缺失变异(外显子9、10、11、12、13缺失)、1个移码变异(p.T260Tfs*10).3例为OCRL基因错义变异(分别为p.1274T、p.1371T、p.F399S).除p.R637X和p.1274T外,其余8例均为新发现的变异.5例患儿行肾活检病理检查,3例表现为局灶性肾小球球性硬化,1例表现为轻度系膜增生性肾炎,1例呈轻微病变;3例患儿伴有局灶性肾小管萎缩及间质纤维化,另2例肾小管间质基本正常;电镜下5例患儿均伴有足突节段轻度融合.结论 儿童Dent病起病隐匿,临床主要表现为低分子量蛋白尿,且多数呈肾病水平蛋白尿,但无低蛋白血症,部分病例不伴有高钙尿症.致病基因大多为CLCN5基因,少数为OCRL基因,基因变异的类型包括错义变异、无义变异、缺失变异及移码变异等.Dent病虽然为肾小管性疾病,但肾活检病理提示多数病例合并肾小球病变.
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