Referenced in: none

Automatically associated channels: ClC4 , ClCK2

Title: Molecular analysis of patients with type III Bartter syndrome: picking up large heterozygous deletions with semiquantitative PCR.

Authors: Kandai Nozu, Xue Jun Fu, Koichi Nakanishi, Norishige Yoshikawa, Hiroshi Kaito, Kyoko Kanda, Rafal Przybyslaw Krol, Ritsuko Miyashita, Hidekazu Kamitsuji, Shoichiro Kanda, Yoshiki Hayashi, Kenichi Satomura, Nobuhiko Shimizu, Kazumoto Iijima, Masafumi Matsuo

Journal, date & volume: Pediatr. Res., 2007 Sep , 62, 364-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17622951

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.