Molecular Analysis of the CLCNKB Gene in Japanese Patients with Classic Bartter Syndrome

Tajima, Toshihiro; Nawate, Mitsuru; Takahashi, Yutaka; Mizoguchi, Yumiko; Sugihara, Shigetaka; Yoshimoto, Masaaki; Murakami, Mutsumi; Adachi, Masanori; Tachibana, Kunihide; Mochizuki, Hidetaka; Fukui, Kenji

doi:10.1507/endocrj.k06-034

Cited by 19 publications

(17 citation statements)

References 23 publications

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“…Further investigation is required to elucidate precise mechanisms in DCT. The mutation: c.1830 G>A in CLCNKB seems to be a founder mutation in Japanese BS type 3 [20]. In comparison to the previous 2 Japanese cases with BS type 3 harbor same mutation having hypocalciuria [21], our case with normocalciuria seems to be contradictory.…”

Section: Discussioncontrasting

confidence: 49%

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Bartter syndrome type 3 in an elderly complicated with adrenocorticotropin-deficiency

et al. 2014

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Section: Discussioncontrasting

confidence: 49%

“…The reason for this discrepancy may be affected with CRF, in which urinary calcium excretion is increased. Considering that our case appears to have late manifestation, the homozygous mutation does not accelerate clinical presentation than heterozygous mutation [20,21].…”

Section: Discussionmentioning

confidence: 65%

Bartter syndrome type 3 in an elderly complicated with adrenocorticotropin-deficiency

et al. 2014

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“…By contrast, several studies in more homogeneous type III BS populations [11–13, 21, 22] showed that whole gene deletions, though observed, tended to be present in compound heterozygosity with point mutations. In particular, Bettinelli found 8 different point mutations and 4 gross deletions in a homogeneous population of mostly Italian patients (the complete deletion of the CLCNKB gene was only found in 23% of patients) [11].…”

Section: Discussionmentioning

confidence: 81%

Poor phenotype-genotype association in a large series of patients with Type III Bartter syndrome

et al. 2017

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IntroductionType III Bartter syndrome (BS) is an autosomal recessive renal tubule disorder caused by loss-of-function mutations in the CLCNKB gene, which encodes the chloride channel protein ClC-Kb. In this study, we carried out a complete clinical and genetic characterization in a cohort of 30 patients, one of the largest series described. By comparing with other published populations, and considering that 80% of our patients presented the p.Ala204Thr Spanish founder mutation presumably associated with a common phenotype, we aimed to test the hypothesis that allelic differences could explain the wide phenotypic variability observed in patients with type III BS.MethodsClinical data were retrieved from the referral centers. The exon regions and flanking intronic sequences of the CLCNKB gene were screened for mutations by polymerase chain reaction (PCR) followed by direct Sanger sequencing. Presence of gross deletions or duplications in the region was checked for by MLPA and QMPSF analyses.ResultsPolyuria, polydipsia and dehydration were the main common symptoms. Metabolic alkalosis and hypokalemia of renal origin were detected in all patients at diagnosis. Calciuria levels were variable: hypercalciuria was detected in 31% of patients, while 23% had hypocalciuria. Nephrocalcinosis was diagnosed in 20% of the cohort. Two novel CLCNKB mutations were identified: a small homozygous deletion (c.753delG) in one patient and a small deletion (c.1026delC) in another. The latter was present in compound heterozygosis with the already previously described p.Glu442Gly mutation. No phenotypic association was obtained regarding the genotype.ConclusionA poor correlation was found between a specific type of mutation in the CLCNKB gene and type III BS phenotype. Importantly, two CLCNKB mutations not previously described were found in our cohort.

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“…Moreover, some previously reported cases possess only heterozygous mutations and another mutations were missing (8,10). Some of these cases may attributable to the methodological problem of direct sequencing.…”

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confidence: 99%

Molecular Analysis of Patients With Type III Bartter Syndrome: Picking Up Large Heterozygous Deletions With Semiquantitative PCR

Nozu

Nakanishi

et al. 2007

Pediatr Res

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Type III Bartter syndrome (BS) (OMIM607364) is caused by mutations in the basolateral chloride channel ClC-Kb gene (CLCNKB). The CLCNKB gene is sometimes reported as having a large deletion mutation, but all cases reported previously were large homozygous deletions and a large heterozygous deletion is impossible to detect by direct sequencing. This report concerns a genetic analysis of five Japanese patients with type III BS. To identify the mutations, we used polymerase chain reaction (PCR) and direct sequencing. To detect large heterozygous deletion mutations of the CLCNKB gene, we conducted semiquantitative PCR amplification using capillary electrophoresis. The result was that four mutations were identified, comprising one novel 2-bp deletion mutation, an entire heterozygous deletion, and a heterozygous deletion mutation of exons 1 and 2. The nonsense mutation W610X was detected in all patients, and this mutation is likely to constitute a founder effect in Japan. Capillary electrophoresis is a new method and extremely useful for detecting large heterozygous deletions, and should be used to examine type III BS cases in whom only a heterozygous mutation has been detected by direct sequencing. This is the first report to identify large heterozygous deletion mutations in the CLCNKB gene in patients with type III BS. (Pediatr Res 62: 364-369, 2007)

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Molecular Analysis of the CLCNKB Gene in Japanese Patients with Classic Bartter Syndrome

Cited by 19 publications

References 23 publications

Bartter syndrome type 3 in an elderly complicated with adrenocorticotropin-deficiency

Bartter syndrome type 3 in an elderly complicated with adrenocorticotropin-deficiency

Poor phenotype-genotype association in a large series of patients with Type III Bartter syndrome

Molecular Analysis of Patients With Type III Bartter Syndrome: Picking Up Large Heterozygous Deletions With Semiquantitative PCR

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