A novel mutation of CLCNKB in a Japanese patient of Gitelman-like phenotype with diuretic insensitivity to thiazide administration

A novel mutation of CLCNKB in a Japanese patient of Gitelman-like phenotype with diuretic insensitivity to thiazide administration

The clinical phenotypes of patients with Bartter syndrome type III sometimes closely resemble those of Gitelman syndrome. We report a patient with mild, adult-onset symptoms, such as muscular weakness and fatigue, who showed hypokalemic metabolic alkalosis, elevated renin–aldosterone levels with nor...

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Main Authors: Ohkubo, Kumiko, Matsuzaki, Tomoe, Yuki, Makiko, Yoshida, Ryoko, Terawaki, Yuichi, Maeyama, Akira, Kawashima, Hironobu, Ono, Junko, Yanase, Toshihiko, Matsunaga, Akira
Format: Online
Language:English
Published: Elsevier 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287957/
id pubmed-4287957
recordtype oai_dc
spelling pubmed-42879572015-01-20 A novel mutation of CLCNKB in a Japanese patient of Gitelman-like phenotype with diuretic insensitivity to thiazide administration Ohkubo, Kumiko Matsuzaki, Tomoe Yuki, Makiko Yoshida, Ryoko Terawaki, Yuichi Maeyama, Akira Kawashima, Hironobu Ono, Junko Yanase, Toshihiko Matsunaga, Akira Article The clinical phenotypes of patients with Bartter syndrome type III sometimes closely resemble those of Gitelman syndrome. We report a patient with mild, adult-onset symptoms, such as muscular weakness and fatigue, who showed hypokalemic metabolic alkalosis, elevated renin–aldosterone levels with normal blood pressure, hypocalciuria and hypomagnesemia. She was also suffering from chondrocalcinosis. A diuretic test with furosemide and thiazide showed a good response to furosemide, but little response to thiazide. Although the clinical findings and diuretic tests predicted that the patient had Gitelman syndrome, genetic analysis found no mutation in SLC12A3. However, a novel missense mutation, p.L647F in CLCNKB, which is located in the CBS domain at the C-terminus of ClC-Kb, was discovered. Therefore, gene analyses of CLCNKB and SLC12A3 might be necessary to elucidate the precise etiology of the salt-losing tubulopathies regardless of the results of diuretic tests. Elsevier 2014-05-04 /pmc/articles/PMC4287957/ /pubmed/25606418 http://dx.doi.org/10.1016/j.mgene.2014.04.005 Text en © 2014 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Ohkubo, Kumiko
Matsuzaki, Tomoe
Yuki, Makiko
Yoshida, Ryoko
Terawaki, Yuichi
Maeyama, Akira
Kawashima, Hironobu
Ono, Junko
Yanase, Toshihiko
Matsunaga, Akira
spellingShingle Ohkubo, Kumiko
Matsuzaki, Tomoe
Yuki, Makiko
Yoshida, Ryoko
Terawaki, Yuichi
Maeyama, Akira
Kawashima, Hironobu
Ono, Junko
Yanase, Toshihiko
Matsunaga, Akira
A novel mutation of CLCNKB in a Japanese patient of Gitelman-like phenotype with diuretic insensitivity to thiazide administration
author_facet Ohkubo, Kumiko
Matsuzaki, Tomoe
Yuki, Makiko
Yoshida, Ryoko
Terawaki, Yuichi
Maeyama, Akira
Kawashima, Hironobu
Ono, Junko
Yanase, Toshihiko
Matsunaga, Akira
author_sort Ohkubo, Kumiko
title A novel mutation of CLCNKB in a Japanese patient of Gitelman-like phenotype with diuretic insensitivity to thiazide administration
title_short A novel mutation of CLCNKB in a Japanese patient of Gitelman-like phenotype with diuretic insensitivity to thiazide administration
title_full A novel mutation of CLCNKB in a Japanese patient of Gitelman-like phenotype with diuretic insensitivity to thiazide administration
title_fullStr A novel mutation of CLCNKB in a Japanese patient of Gitelman-like phenotype with diuretic insensitivity to thiazide administration
title_full_unstemmed A novel mutation of CLCNKB in a Japanese patient of Gitelman-like phenotype with diuretic insensitivity to thiazide administration
title_sort novel mutation of clcnkb in a japanese patient of gitelman-like phenotype with diuretic insensitivity to thiazide administration
description The clinical phenotypes of patients with Bartter syndrome type III sometimes closely resemble those of Gitelman syndrome. We report a patient with mild, adult-onset symptoms, such as muscular weakness and fatigue, who showed hypokalemic metabolic alkalosis, elevated renin–aldosterone levels with normal blood pressure, hypocalciuria and hypomagnesemia. She was also suffering from chondrocalcinosis. A diuretic test with furosemide and thiazide showed a good response to furosemide, but little response to thiazide. Although the clinical findings and diuretic tests predicted that the patient had Gitelman syndrome, genetic analysis found no mutation in SLC12A3. However, a novel missense mutation, p.L647F in CLCNKB, which is located in the CBS domain at the C-terminus of ClC-Kb, was discovered. Therefore, gene analyses of CLCNKB and SLC12A3 might be necessary to elucidate the precise etiology of the salt-losing tubulopathies regardless of the results of diuretic tests.
publisher Elsevier
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287957/
_version_ 1613174554202472448

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