Two siblings (brother and sister) with renal tubular hypokalemic alkalosis underwent clinical, biochemical and molecular investigations. Although the biochemical findings were similar (including hypokalemia, metabolic...Two siblings (brother and sister) with renal tubular hypokalemic alkalosis underwent clinical, biochemical and molecular investigations. Although the biochemical findings were similar (including hypokalemia, metabolic alkalosis, hyperreninemia, hyperaldosteronism and normal blood pressure), the clinical findings were different: the boy, who also presented syndromic signs, developed glomerular proteinuria and renal biopsy revealed focal segmental glomerular sclerosis; the girl showed the typical signs of classic Bartter syndrome. As described in a previous paper, a heterozygous mutation (frameshift 2534delT) was demonstrated in the gene encoding the thiazide- sensitive NaCl co- transporter (SLC12A3) of the distal convoluted tubule; the second molecular analysis revealed a compound heterozygous mutation (A61D/V149E) in the CLCNKB chloride channel gene in both subjects, inherited in trans from the parents. The childrenwere finally diagnosed as having classic Bartter syndrome. These cases represent the first report of the simultaneous presence of heterozygous and compound heterozygous mutations in the SLC12A3 and CLCNKB genes, both of which are involved in renal salt losing tubulopathies, and confirm previous observations regarding classic Bartter syndrome phenotype variability in the same kindred.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
Bartter syndrome type Ⅲ is a Bartter syndrome subtype, which has a group of autosomal-recessive inherited disorders with clinical characteristics such as renal salt wasting, hypokalemic metabolic alkalosis,elevated r...Bartter syndrome type Ⅲ is a Bartter syndrome subtype, which has a group of autosomal-recessive inherited disorders with clinical characteristics such as renal salt wasting, hypokalemic metabolic alkalosis,elevated renin and aldosterone levels, with normal or low blood pressure.1 Unlike other subtypes that often begin in the neonatal period, type Ⅲ, due to mutations in the CLCNKB gene,2-4 is highly variable and usually presents as a ＂classic＂ Barrter variant characterized by an onset in early childhood and less severe or absent hypercalciuria and nephrocalcinosis.展开更多
文摘Two siblings (brother and sister) with renal tubular hypokalemic alkalosis underwent clinical, biochemical and molecular investigations. Although the biochemical findings were similar (including hypokalemia, metabolic alkalosis, hyperreninemia, hyperaldosteronism and normal blood pressure), the clinical findings were different: the boy, who also presented syndromic signs, developed glomerular proteinuria and renal biopsy revealed focal segmental glomerular sclerosis; the girl showed the typical signs of classic Bartter syndrome. As described in a previous paper, a heterozygous mutation (frameshift 2534delT) was demonstrated in the gene encoding the thiazide- sensitive NaCl co- transporter (SLC12A3) of the distal convoluted tubule; the second molecular analysis revealed a compound heterozygous mutation (A61D/V149E) in the CLCNKB chloride channel gene in both subjects, inherited in trans from the parents. The childrenwere finally diagnosed as having classic Bartter syndrome. These cases represent the first report of the simultaneous presence of heterozygous and compound heterozygous mutations in the SLC12A3 and CLCNKB genes, both of which are involved in renal salt losing tubulopathies, and confirm previous observations regarding classic Bartter syndrome phenotype variability in the same kindred.
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。
文摘Bartter syndrome type Ⅲ is a Bartter syndrome subtype, which has a group of autosomal-recessive inherited disorders with clinical characteristics such as renal salt wasting, hypokalemic metabolic alkalosis,elevated renin and aldosterone levels, with normal or low blood pressure.1 Unlike other subtypes that often begin in the neonatal period, type Ⅲ, due to mutations in the CLCNKB gene,2-4 is highly variable and usually presents as a ＂classic＂ Barrter variant characterized by an onset in early childhood and less severe or absent hypercalciuria and nephrocalcinosis.
