Patients With Biallelic Mutations in the Chloride Channel Gene CLCNKB: Long-Term Management and Outcome

Bettinelli, Alberto; Borsa, Nicolò; Bellantuono, R; Syrén, Marie Louise; Calabrese, Raffaele; Edefonti, Alberto; Komninos, John; Santostefano, Marisa; Beccaria, Luciano; Pela, Ivana; Bianchetti, Mario G.; Tedeschi, Silvana

doi:10.1053/j.ajkd.2006.10.001

Cited by 57 publications

(63 citation statements)

References 23 publications

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“…22,[24][25][26] Tseng et al 24 reported that 7 of 117 patients (6%) with genetically diagnosed GS developed chronic kidney disease (stage III or IV). In this study 12 of 30 patients (40.0%) with type III BS, 11 of 90 (12.0%) with GS, and 27 of 43 (62.8%) with p-BS/GS presented with stage II-IV chronic kidney disease.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…When compared with these types of Bartter syndrome, patients with CLCNKB mutations often experience a less pronounced disease phenotype. Symptoms are usually detected at later ages and are often manageable with supportive treatment (20). The less severe phenotype of Bartter syndrome type III might be the result of the existence of an additional basolateral chloride efflux pathway, the potassium-chloride cotransporter KCC4, in the thick ascending limb of Henle (21), which might partly compensate loss of function of hClC-Kb channels.…”

Section: Affected Kidneys and The Clinical Symptoms Of Bartter Syndromentioning

confidence: 99%

“…Many of those result in truncations of the cytosolic carboxyl terminus within or nearby the two conserved cystathionine-␤-synthase domains (CBS1 and CBS2) (20,(23)(24)(25). One of these truncation mutations, W610X hClC-Kb, is among the most prevalent CLCNKB mutations in asian populations (23)(24)(25).…”

Section: Affected Kidneys and The Clinical Symptoms Of Bartter Syndromentioning

confidence: 99%

Carboxyl-terminal Truncations of ClC-Kb Abolish Channel Activation by Barttin Via Modified Common Gating and Trafficking

Stölting

Bungert-Plümke

Franzen

et al. 2015

Journal of Biological Chemistry

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Background: Carboxyl-terminal truncations of hClC-Kb cause Bartter syndrome. Results: hClC-Kb channels lacking the carboxyl terminus still associate with barttin, but are neither stabilized in the membrane nor activated. Conclusion: Truncated hClC-Kb channels are not regulated by barttin. Significance: Elucidating the role of the carboxyl terminus of hClC-Kb significantly improves our understanding of CLC-K regulation by barttin.

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“…Long-term follow-up of patients with classic Bartter syndrome secondary to biallelic mutations in CLCNKB showed mild to moderate glomerular proteinuria in 6/13 patients, with associated microhaematuria in two of the six patients. Renal biopsy performed in two patients revealed mesangial expansion/hypertrophy without juxtaglomerular apparatus hypertrophy [10]. No ultrastructural examination of the glomeruli was reported.…”

Section: Discussionmentioning

confidence: 99%

Gitelman syndrome and glomerular proteinuria: a link between loss of sodium-chloride cotransporter and podocyte dysfunction?

Demoulin

Aydın

Cosyns

et al. 2014

Nephrology Dialysis Transplantation

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We report on a 27-year-old patient presenting with chronic hypokalaemia, inappropriate kaliuresis, hypomagnesaemia and alkalosis, associated with moderate proteinuria. Genetic analysis evidenced a homozygous mutation ( p.Arg399Cys) in the SLC12A3 gene coding for the sodium-chloride cotransporter (NCC), confirming the diagnosis of Gitelman syndrome. Further genetic testing did not show any mutation in NPHS2. A renal biopsy was performed in view of the unusual association with proteinuria. Light microscopy showed hypertrophy of the juxtaglomerular apparatus and discrete mesangial thickening. In addition to possible focal segmental glomerular sclerosis lesions, electron microscopy showed extensive segments of variably thickened glomerular basement membrane (GBM), contrasting with segments of regular GBM of low range thickness, and effacement of podocyte foot processes. Of interest, alterations of the GBM were also observed in a Slc12a3 knock-out mouse model for Gitelman syndrome. These data suggest that the association between Gitelman syndrome and secondary changes of the GBM is probably not coincidental. Possible mechanisms include angiotensin II-or renin-induced podocyte lesions, as well as chronic hypokalaemia.

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Patients With Biallelic Mutations in the Chloride Channel Gene CLCNKB: Long-Term Management and Outcome

Cited by 57 publications

References 23 publications

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

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

Carboxyl-terminal Truncations of ClC-Kb Abolish Channel Activation by Barttin Via Modified Common Gating and Trafficking

Gitelman syndrome and glomerular proteinuria: a link between loss of sodium-chloride cotransporter and podocyte dysfunction?

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