[Show abstract][Hide abstract] ABSTRACT: Type III Bartter syndrome (BS) (OMIM607364) is caused by mutations in the basolateral chloride channel CIC-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.
Pediatric Research 10/2007; 62(3):364-9. · 2.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bartter's and Gitelman's syndromes are characterized by hypokalemia, normal to low blood pressure and hypochloremic metabolic alkalosis. Recently, investigators have been able to demonstrate mutations of six genes encoding several renal tubular transporters and ion channels that can be held responsible for Bartter's and Gitelman's syndromes. Neonatal Bartter's syndrome is caused by mutations of NKCC2 or ROMK, classic Bartter's syndrome by mutations of ClC-Kb, Bartter's syndrome associated with sensorineural deafness is due to mutations of BSND, Gitelman's syndrome to mutations of NCCT and Bartter's syndrome associated with autosomal dominant hypocalcemia is linked to mutations of CASR. We review the pathophysiology of these syndromes in relation to their clinical presentation.
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