Bartter and Gitelman syndromes(BS and GS) are inherited disorders resulting in defects in renal tubularhandling of sodium,potassium and chloride.Previously considered as genotypic and phenotypic heterogeneous diseases...Bartter and Gitelman syndromes(BS and GS) are inherited disorders resulting in defects in renal tubularhandling of sodium,potassium and chloride.Previously considered as genotypic and phenotypic heterogeneous diseases,recent evidence suggests that they constitute a spectrum of disease caused by different genetic mutations with the molecular defects of chloride reabsorption originating at different sites of the nephron in each condition.Although they share some characteristic metabolic abnormalities such as hypokalemia,metabolic alkalosis,hyperplasia of the juxtaglomerular apparatus with hyperreninemia,hyperaldosteronism,the clinical and laboratory manifestations may not always allow distinction between them.Diuretics tests,measuring the changes in urinary fractional excretion of chloride from baseline after administration of either hydrochlorothiazide or furosemide show very little change(< 2.3%) in the fractional excretion of chloride from baseline in GS when compared with BS,except when BS is associated with KCNJ1 mutations where a good response to both diuretics exists.The diuretic test is not recommended for infants or young children with suspected BS because of a higher risk of volume depletion in such children.Clinical symptoms and biochemical markers of GS and classic form of BS(type III) may overlap and thus genetic analysis may specify the real cause of symptoms.However,although genetic analysis is available,its use remains limited because of limited availability,large gene dimensions,lack of hot-spot mutations,heavy workup time and costs involved.Furthermore,considerable overlap exists between the different genotypes and phenotypes.Although BS and GS usually have distinct presentations and are associated with specific gene mutations,there remains considerable overlap between their phenotypes and genotypes.Thus,they are better described as a spectrum of clinical manifestations caused by different gene mutations.展开更多
目的分析中国42例3型巴特综合征(Bartter syndrome type 3,BS3)患儿的CLCNKB基因变异,探讨基因型与临床表型的特点。方法42例经基因检测确诊的BS3病例来自2012年6月至2018年10月青岛大学附属医院和青岛大学附属市立医院收治的患儿,分别...目的分析中国42例3型巴特综合征(Bartter syndrome type 3,BS3)患儿的CLCNKB基因变异,探讨基因型与临床表型的特点。方法42例经基因检测确诊的BS3病例来自2012年6月至2018年10月青岛大学附属医院和青岛大学附属市立医院收治的患儿,分别来自40个汉族家系和1个回族家系。采用二代测序和多重连接酶探针依赖扩增(MLPA)技术分析BS3患儿的CLCNKB基因变异及其特点。收集患儿临床资料,观察和随访药物治疗疗效和生长发育改善的情况。根据基因变异的严重程度将患儿分为2组:严重变异基因型组(严重变异组,n=26)和轻度变异基因型组(轻度变异组,n=12)。比较两组患儿的临床表型特征。结果42例BS3患儿的二代测序和MLPA分析共确定CLCNKB基因36个变异,其中16个为新发现变异。CLCNKB基因大片段缺失频率高达55%,全基因缺失达40%,全基因缺失是最常见的基因突变类型。患儿最常见的临床表现为生长迟缓(38/42)、多饮多尿(35/42)、便秘(31/42)和呕吐(27/42)。42例患儿均表现为低钾低氯代谢性碱中毒。经氯化钾和吲哚美辛为基础的药物治疗后,大部分患儿的生长发育和电解质紊乱得到明显改善。与轻度变异组相比,严重变异组表现出更严重的代谢性碱中毒。结论本研究发现CLCNKB基因36个变异,其中16个为新变异,丰富了人类基因突变库,为BS3的诊治以及中国巴特综合征人群遗传咨询的开展提供了有益的借鉴。展开更多
文摘Bartter and Gitelman syndromes(BS and GS) are inherited disorders resulting in defects in renal tubularhandling of sodium,potassium and chloride.Previously considered as genotypic and phenotypic heterogeneous diseases,recent evidence suggests that they constitute a spectrum of disease caused by different genetic mutations with the molecular defects of chloride reabsorption originating at different sites of the nephron in each condition.Although they share some characteristic metabolic abnormalities such as hypokalemia,metabolic alkalosis,hyperplasia of the juxtaglomerular apparatus with hyperreninemia,hyperaldosteronism,the clinical and laboratory manifestations may not always allow distinction between them.Diuretics tests,measuring the changes in urinary fractional excretion of chloride from baseline after administration of either hydrochlorothiazide or furosemide show very little change(< 2.3%) in the fractional excretion of chloride from baseline in GS when compared with BS,except when BS is associated with KCNJ1 mutations where a good response to both diuretics exists.The diuretic test is not recommended for infants or young children with suspected BS because of a higher risk of volume depletion in such children.Clinical symptoms and biochemical markers of GS and classic form of BS(type III) may overlap and thus genetic analysis may specify the real cause of symptoms.However,although genetic analysis is available,its use remains limited because of limited availability,large gene dimensions,lack of hot-spot mutations,heavy workup time and costs involved.Furthermore,considerable overlap exists between the different genotypes and phenotypes.Although BS and GS usually have distinct presentations and are associated with specific gene mutations,there remains considerable overlap between their phenotypes and genotypes.Thus,they are better described as a spectrum of clinical manifestations caused by different gene mutations.
文摘目的分析中国42例3型巴特综合征(Bartter syndrome type 3,BS3)患儿的CLCNKB基因变异,探讨基因型与临床表型的特点。方法42例经基因检测确诊的BS3病例来自2012年6月至2018年10月青岛大学附属医院和青岛大学附属市立医院收治的患儿,分别来自40个汉族家系和1个回族家系。采用二代测序和多重连接酶探针依赖扩增(MLPA)技术分析BS3患儿的CLCNKB基因变异及其特点。收集患儿临床资料,观察和随访药物治疗疗效和生长发育改善的情况。根据基因变异的严重程度将患儿分为2组:严重变异基因型组(严重变异组,n=26)和轻度变异基因型组(轻度变异组,n=12)。比较两组患儿的临床表型特征。结果42例BS3患儿的二代测序和MLPA分析共确定CLCNKB基因36个变异,其中16个为新发现变异。CLCNKB基因大片段缺失频率高达55%,全基因缺失达40%,全基因缺失是最常见的基因突变类型。患儿最常见的临床表现为生长迟缓(38/42)、多饮多尿(35/42)、便秘(31/42)和呕吐(27/42)。42例患儿均表现为低钾低氯代谢性碱中毒。经氯化钾和吲哚美辛为基础的药物治疗后,大部分患儿的生长发育和电解质紊乱得到明显改善。与轻度变异组相比,严重变异组表现出更严重的代谢性碱中毒。结论本研究发现CLCNKB基因36个变异,其中16个为新变异,丰富了人类基因突变库,为BS3的诊治以及中国巴特综合征人群遗传咨询的开展提供了有益的借鉴。
