Analysis of claudin genes in pediatric patients with Bartter's syndrome.
Analysis of claudin genes in pediatric patients with Bartter's syndrome.
复制标题
DOI：
10.1111/j.1749-6632.2009.04031.x
复制
发表时间：
2009-05
影响因子：
5.2
通讯作者：
Lu Q
中科院分区：
文献类型：
--
作者：
Chen YH;Lin JJ;Jeansonne BG;Tatum R;Lu Q
巴特综合征是一系列症状，其特征是高肾素血症性低钾血症、代谢性碱中毒、肾素和醛固酮升高、血压低或正常以及肾小球旁器官增生。到目前为止，已经描述了调节亨利袢粗升肢氯化钠转运的蛋白质的五种基因突变。然而，其中一些患者出现低镁血症的分子机制仍不清楚。紧密连接蛋白是紧密连接内的跨膜蛋白家族，已被证明对离子的旁细胞运动很重要。家族性低镁血症伴高钙尿症和肾钙质沉着症患者中已发现claudin-16 突变。为了检验紧密蛋白基因突变可能与巴特综合征中镁和钙转运改变有关的假设，我们开始检查四名巴特综合征儿科患者肾小管中已知存在的紧密蛋白基因。所有四名患者都是患有低镁血症和高钙尿症的非裔美国人。在这项研究中，我们没有发现这些患者的claudin-2、-3、-4、-7、-8、-10、-11或-16基因编码区有任何突变。然而，所有患者在claudin-8基因序列的451位点均发生单核苷酸C取代T，从而将claudin-8蛋白第二胞外结构域151位的氨基酸残基从丝氨酸变为脯氨酸。这种已知的单核苷酸多态性的意义仍有待确定。
Bartter’s syndrome is a constellation of symptoms characterized by hyper-reninemic hypokalemia, metabolic alkalosis, elevated renin and aldosterone, low or normal blood pressure, and hyperplasia of the juxtaglomerular apparatus. So far, five gene mutations in proteins regulating the sodium chloride transport in the thick ascending limb of Henle’s loop have been described. However, the molecular mechanisms underlying the presentation of hypomagnesemia in some of these patients remains unclear. Claudins are a family of transmembranous proteins within the tight junctions that have been shown to be important for the paracellular movement of ions. Mutations in claudin-16 have been identified in patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis. To test the hypothesis that mutations in claudin genes may be involved in the altered magnesium and calcium transport in Bartter’s syndrome, we began to examine the genes of claudins known to be present in renal tubules in four pediatric patients with Bartter’s syndrome. All four patients were African Americans with hypomagnesemia and hypercalciuria. In this study, we did not find any mutation in the coding regions of claudin-2, -3, -4, -7, -8, -10, -11, or -16 genes in these patients. However, all patients had a single nucleotide substitution of C for T at the position of 451 of claudin-8 gene sequence that changes amino acid residue from serine to proline at the position of 151 in the second extracellular domain of claudin-8 protein. The significance of this known single nucleotide polymorphism remains to be determined.
登录
查看更多内容
影响因子：
5.5
作者：
Angelow, S;Kim, KJ;Yu, ASL
通讯作者：
Yu, ASL
影响因子：
30.8
作者：
Simon, DB;Bindra, RS;Lifton, RP
通讯作者：
Lifton, RP
通过表达突变型紧密连接膜蛋白，细胞旁通透性和跨上皮电阻的功能性分离以及顶端-基底外侧膜内扩散屏障的破坏。
影响因子：
7.8
作者：
Balda, M S;Whitney, J A;Flores, C;Gonzalez, S;Cereijido, M;Matter, K
通讯作者：
Matter, K
影响因子：
19.6
作者：
Reyes, JL;Lamas, M;González-Mariscal, L
通讯作者：
González-Mariscal, L
影响因子：
5.1
作者：
SEYBERTH, HW;RASCHER, W;SCHARER, K
通讯作者：
SCHARER, K