Barttin is a Cl- channel β-subunit crucial for renal Cl- reabsorption and inner ear K+ secretion

Estévez, Raúl; Boettger, Thomas; Stein, Valentin; Birkenhäger, Ralf; Otto, Edgar A.; Hildebrandt, Friedhelm; Jentsch, Thomas J.

doi:10.1038/35107099

Cited by 523 publications

(678 citation statements)

References 28 publications

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“…These genes appear to play a role, to varying degrees, in K + recirculation in the inner ear (Estevez et al 2001;Liu et al 2001;Wangemann 2002;Nicolas et al 2003). We found higher levels of Gja1 transcripts in the SG and LW compared with the OC.…”

Section: Discussionmentioning

confidence: 99%

Differential Expression of Genes within the Cochlea as Defined by a Custom Mouse Inner Ear Microarray

Morris

Snir²,

Pompéia

et al. 2005

JARO

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Microarray analyses have contributed greatly to the rapid understanding of functional genomics through the identification of gene networks as well as gene discovery. To facilitate functional genomics of the inner ear, we have developed a mouse inner-earpertinent custom microarray chip (CMA-IE1). Nonredundant cDNA clones were obtained from two cDNA library resources: the RIKEN subtracted inner ear set and the NIH organ of Corti library. At least 2000 cDNAs unique to the inner ear were present on the chip. Comparisons were performed to examine the relative expression levels of these unique cDNAs within the organ of Corti, lateral wall, and spiral ganglion. Total RNA samples were obtained from the three cochlear-dissected fractions from adult CF-1 mice. The total RNA was linearly amplified, and a dendrimer-based system was utilized to enhance the hybridization signal. Differentially expressed genes were verified by comparison to known gene expression patterns in the cochlea or by correlation with genes and gene families deduced to be present in the three tissue types. Approximately 22Y25% of the genes on the array had significant levels of expression. A number of differentially expressed genes were detected in each tissue fraction. These included genes with known functional roles, hypothetical genes, and various unknown or uncharacterized genes. Four of the differentially expressed genes found in the organ of Corti are linked to deafness loci. None of these are hypothetical or unknown genes.

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Section: Discussionmentioning

confidence: 99%

Differential Expression of Genes within the Cochlea as Defined by a Custom Mouse Inner Ear Microarray

Morris

Snir²,

Pompéia

et al. 2005

JARO

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“…Recently, a new gene (BSND) responsible for the antenatal variant of Bartter syndrome with sensorineural deafness has been identified (27). This new gene encodes a new protein, barttin, which acts as an essential ␤-subunit for basolateral ClC-ka and ClC-kb channels (28). Proband 1 presented with all of the features of classical Bartter syndrome.…”

Section: Discussionmentioning

confidence: 99%

Functional Characterization of a Calcium-Sensing Receptor Mutation in Severe Autosomal Dominant Hypocalcemia with a Bartter-Like Syndrome

Vargas‐Poussou¹,

Huang²,

Hulin³

et al. 2002

Journal of the American Society of Nephrology

312

195

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Abstract. The extracellular Ca 2ϩ -sensing receptor (CaSR) plays an essential role in extracellular Ca 2ϩ homeostasis by regulating the rate of parathyroid hormone (PTH) secretion and the rate of calcium reabsorption by the kidney. Activation of the renal CaSR is thought to inhibit paracellular divalent cation reabsorption in the cortical ascending limb (cTAL) both directly and indirectly via a decrease in NaCl transport. However, in patients with autosomal dominant hypocalcemia (ADH), caused by CaSR gain-of-function mutations, a defect in tubular NaCl reabsorption with renal loss of NaCl has not been described so far. This article describes a patient with ADH due to a gain-of-function mutation in the CaSR, L125P, associated with a Bartter-like syndrome that is characterized by a decrease in distal tubular fractional chloride reabsorption rate and negative NaCl balance with secondary hyperaldosteronism and hypokalemia. The kinetics of activation of the L125P mutant receptor expressed in HEK-293 cells, assessed by measuring CaSR-stimulated changes in intracellular Ca 2ϩ and ERK activity, showed a dramatic reduction in the EC 50 for extracellular Ca 2ϩ compared with the wild-type and a loss-offunction mutant CaSR (I40F). This study describes the first case of ADH associated with a Bartter-like syndrome. It is herein proposed that the L125P mutation of the CaSR, which represents the most potent gain-of-function mutation reported so far, may reduce NaCl reabsorption in the cTAL sufficiently to result in renal loss of NaCl with secondary hyperaldosteronism and hypokalemia.

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“…Mutations in these genes lead to types I-IV BS, respectively. 6,8 Combined mutations in both CLCNKA and CLCNKB result in type IVb BS. 9,10 By contrast, mutations in the SLC12A3 gene, which encodes the apical thiazide-sensitive Na-Cl cotransporter (NCCT) in the distal convoluted tubule, are responsible for GS.…”

Section: Introductionmentioning

confidence: 99%

Differential diagnosis of Bartter syndrome, Gitelman syndrome, and pseudo–Bartter/Gitelman syndrome based on clinical characteristics

Matsunoshita

Nozu

Shono

et al. 2016

Genetics in Medicine

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Purpose: Phenotypic overlap exists among type III Bartter syndrome (BS), Gitelman syndrome (GS), and pseudo-BS/GS (p-BS/ GS), which are clinically difficult to distinguish. We aimed to clarify the differences between these diseases, allowing accurate diagnosis based on their clinical features. Methods:A total of 163 patients with genetically defined type III BS (n = 30), GS (n = 90), and p-BS/GS (n = 43) were included. Age at diagnosis, sex, body mass index, estimated glomerular filtration rate, and serum and urine electrolyte concentrations were determined. Results:Patients with p-BS/GS were significantly older at diagnosis than those with type III BS and GS. Patients with p-BS/GS included a significantly higher percentage of women and had a lower body mass index and estimated glomerular filtration rate than did patients with GS. Although hypomagnesemia and hypocalciuria were predominant biochemical findings in patients with GS, 17 and 23% of patients with type III BS and p-BS/GS, respectively, also showed these abnormalities. Of patients with type III BS, GS, and p-BS/GS, 40, 12, and 63%, respectively, presented with chronic kidney disease.

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Barttin is a Cl- channel β-subunit crucial for renal Cl- reabsorption and inner ear K+ secretion

Cited by 523 publications

References 28 publications

Differential Expression of Genes within the Cochlea as Defined by a Custom Mouse Inner Ear Microarray

Differential Expression of Genes within the Cochlea as Defined by a Custom Mouse Inner Ear Microarray

Functional Characterization of a Calcium-Sensing Receptor Mutation in Severe Autosomal Dominant Hypocalcemia with a Bartter-Like Syndrome

Differential diagnosis of Bartter syndrome, Gitelman syndrome, and pseudo–Bartter/Gitelman syndrome based on clinical characteristics

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