Novel SLC12A3 mutations in Chinese patients with Gitelman's syndrome
Novel SLC12A3 mutations in Chinese patients with Gitelman's syndrome
复制标题
中国 Gitelman 综合征患者中的新 SLC12A3 突变
DOI：
10.1159/000117815
复制
发表时间：
2008-01-01
影响因子：
--
通讯作者：
Chen, Nan
中科院分区：
文献类型：
--
作者：
Shao, Leping;Ren, Hong;Chen, Nan
背景资料：SLC 12 A3基因的失活突变是吉特尔曼综合征（GS）的最常见原因，吉特尔曼综合征是一种以常染色体隐性遗传特征遗传的疾病。在少数情况下，GS样表型由CLCNKB基因突变引起。研究方法：我们寻找SLC 12 A3和CLCNKB基因突变13例中国患者（9男4女，年龄35 - 8 - 14岁）8个无关的家庭与GS的临床和生化特征。所有编码区，包括内含子-外显子边界，使用PCR进行分析，然后进行直接序列分析。结果：我们发现了10个突变分布在整个SLC 12 A3基因。其中7个是新的变异体，包括4个错义突变（Gly 196 Val，Cys 430 Gly，Gly 439 Val和Leu 571 Pro），2个缺失（1384 delG和346- 353 delACTGATGG）和1个框内插入（997 insCys）。3个突变复发，包括2个错义突变（Thr 60 Met和Asp 486 Asn）和1个缺失（2883- 2884 delAG）。13例患者中8例为Thr 60 Met纯合或杂合突变。在CLCNKB基因中未检测到突变。结论：Thr 60 Met可能是中国GS患者最常见的突变。可能的特定基因型-表型相关性很难确定。版权所有（c）2008 S. Karger AG，巴塞尔。
Background: Inactivating mutations of the SLC12A3 gene are the most common cause of Gitelman's syndrome (GS), a disorder inherited as an autosomal recessive trait. In a minority of cases, GS-like phenotypes are caused by mutations in the CLCNKB gene. Methods: We searched for SLC12A3 and CLCNKB gene mutations in 13 Chinese patients (9 males and 4 females, age 35 8 14 years) from 8 unrelated families with the clinical and biochemical features of GS. All coding regions, including intron-exon boundaries, were analyzed using PCR followed by direct sequence analysis. Results: We identified 10 mutations distributed throughout the SLC12A3 gene. Seven are novel variants, including 4 missense mutations (Gly196Val, Cys430Gly, Gly439Val and Leu571Pro), 2 deletions (1384delG and 346-353delACTGATGG) and 1 inframe insertion (997insCys). Three mutations were recurrent, including 2 missense mutations (Thr60Met and Asp486Asn) and 1 deletion (2883-2884delAG). The homozygous or heterozygous mutation Thr60Met was found in 8 of 13 patients. There were no mutations detected in the CLCNKB gene. Conclusions: Thr60Met may be the most common mutation in Chinese patients with GS. Possible specific genotype-phenotype correlations were difficult to identify. Copyright (c) 2008 S. Karger AG, Basel.