Tajima Toshihiro, Nawate Mitsuru, Takahashi Yutaka, Mizoguchi Yumiko, Sugihara Shigetaka, Yoshimoto Masaaki, Murakami Mutsumi, Adachi Masanori, Tachibana Katsuhiko, Mochizuki Hiroshi, Fujieda Kenji
Department of Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan.
Endocr J. 2006 Oct;53(5):647-52. doi: 10.1507/endocrj.k06-034. Epub 2006 Aug 11.
Deletions or mutations in the gene encoding the basolateral chloride channel CLC-Kb (CLCNKB) cause classic Bartter syndrome (MIM 602023), which is characterized by hypokalemic metabolic alkalosis, hyperreninemic hyperaldosteronism and hypercalciura. These patients are usually diagnosed during infancy or childhood due to failure to thrive and growth retardation. The purpose of this study was to investigate the underlying mutations in Japanese patients with classic Bartter syndrome. Seven Japanese patients from seven different families diagnosed as having classic Bartter syndrome were studied. Analysis of CLCNKB demonstrated a large deletion in two patients, a partial deletion in one patient and two mutations (DeltaL130 in exon 4 and W610X in exon 16) in the remaining four patients. DeltaL130 is a novel mutation, but W610X was previously reported in three unrelated Japanese patients. Six out of the seven patients were diagnosed due to typical characteristics of classic Bartter syndrome such as failure to thrive and poor weight gain however, one patient was asymptomatic with mild hypokalemia. In conclusion, we identified a novel mutation of the CLCNKB gene, DeltaL130. We did not determine whether the W610X mutation in our patients was from a common ancestor or if this mutation is frequent in Japan.
编码基底外侧氯通道CLC-Kb（CLCNKB）的基因发生缺失或突变会导致经典型巴特综合征（MIM 602023），其特征为低钾血症性代谢性碱中毒、高肾素血症性醛固酮增多症和高钙尿症。这些患者通常在婴儿期或儿童期因生长发育不良和发育迟缓而被诊断出来。本研究的目的是调查日本经典型巴特综合征患者的潜在突变情况。对来自七个不同家庭的七名被诊断为经典型巴特综合征的日本患者进行了研究。对CLCNKB的分析显示，两名患者存在大片段缺失，一名患者存在部分缺失，其余四名患者存在两个突变（外显子4中的DeltaL130和外显子16中的W610X）。DeltaL130是一种新的突变，但W610X此前曾在三名无亲缘关系的日本患者中报道过。七名患者中有六名因经典型巴特综合征的典型特征如生长发育不良和体重增加不佳而被诊断出来，然而，有一名患者无症状，仅有轻度低钾血症。总之，我们鉴定出了CLCNKB基因的一种新突变DeltaL130。我们尚未确定我们患者中的W610X突变是否来自共同祖先，也未确定该突变在日本是否常见。
