Identification and functional analysis of novel mutations of the CLCNKB gene in Chinese patients with classic Bartter syndrome

CORC > 上海神经科学研究所 > 中国科学院上海生命科学研究院神经科学研究所 > 神经所(总)

	Identification and functional analysis of novel mutations of the CLCNKB gene in Chinese patients with classic Bartter syndrome
	Yu, Y. ; Xu, C. ; Pan, X. ; Ren, H. ; Wang, W. ; Meng, X. ; Huang, F. ; Chen, N.
刊名	CLINICAL GENETICS
	2010
卷号	77 期号:2 页码:155-162
关键词	Bartter syndrome ClC-Kb CLCNKB mutation CHLORIDE CHANNEL GENE CALCIUM-SENSING RECEPTOR SYNDROME TYPE-III CL TRANSPORT HENLE LOOP INNER-EAR KB GENE GITELMAN KIDNEY
ISSN号	0009-9163
通讯作者	Chen, N (reprint author), Shanghai Ruijin Hosp, Dept Nephrol, 197 Rui Jin Er Rd, Shanghai 200025, Peoples R China,chen.doc@163.com
英文摘要	Mutations in the gene CLCNKB encoding the ClC-Kb chloride channel causes classic Bartter syndrome, which is characterized by hypokalaemic metabolic alkalosis, renal salt loss, hyper-reninaemic hyperaldosteronism and normal blood pressure. We aimed to investigate the underlying mutations in CLCNKB in two Chinese patients with classic Bartter syndrome and then test the effect of the mutations on ClC-Kb chloride channel activity. Mutation analysis of CLCNKB was performed by polymerase chain reaction (PCR) direct sequencing. Expression of the wild-type and mutant ClC-Kb was heterologous in Xenopus laevis oocytes. We identified three novel CLCNKB gene mutations, including one homozygous missense mutation (R351W) in one patient and two compound heterozygous mutations (R30X and A210V) in the other. As determined by two-electrode voltage-clamp analysis of ClC-Kb channel activity, R30X abolished the current amplitude; A210V and R351W significantly reduced the current amplitude. A210V was almost as sensitive as the wild type to extracellular pH and calcium, whereas R351W removed extracellular calcium activation and markedly reduced alkaline pH activation of ClC-Kb. The three novel CLCNKB mutations we identified in two Chinese patients with classic Bartter syndrome have a role in altering the functional properties of ClC-Kb channels.
学科主题	Genetics & Heredity
收录类别	SCI
资助信息	National Natural Scientific Foundation, China[30670972]
语种	英语
公开日期	2012-07-13
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/1619]
专题	上海神经科学研究所_神经所(总)
推荐引用方式 GB/T 7714	Yu, Y.,Xu, C.,Pan, X.,et al. Identification and functional analysis of novel mutations of the CLCNKB gene in Chinese patients with classic Bartter syndrome[J]. CLINICAL GENETICS,2010,77(2):155-162.
APA	Yu, Y..,Xu, C..,Pan, X..,Ren, H..,Wang, W..,...&Chen, N..(2010).Identification and functional analysis of novel mutations of the CLCNKB gene in Chinese patients with classic Bartter syndrome.CLINICAL GENETICS,77(2),155-162.
MLA	Yu, Y.,et al."Identification and functional analysis of novel mutations of the CLCNKB gene in Chinese patients with classic Bartter syndrome".CLINICAL GENETICS 77.2(2010):155-162.