Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 May 4:2:342-8.
doi: 10.1016/j.mgene.2014.04.005. eCollection 2014 Dec.

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

Kumiko Ohkubo  1 , Tomoe Matsuzaki  2 , Makiko Yuki  2 , Ryoko Yoshida  3 , Yuichi Terawaki  3 , Akira Maeyama  4 , Hironobu Kawashima  2 , Junko Ono  5 , Toshihiko Yanase  3 , Akira Matsunaga  1
Affiliations

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

Kumiko Ohkubo et al. Meta Gene. .

Abstract

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.

Keywords: Bartter syndrome type III; CLCNKB; Chondrocalcinosis; ClC-Kb; Gitelman syndrome; Hydrochlorothiazide.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Conventional radiography of the antero-posterior view of pelvis in the patient.
Fig. 2
Fig. 2
Gene analysis by direct sequencing of the PCR product of exon 19 in CLCNKB in the patient.
Fig. 3
Fig. 3
The amino-acid sequence alignment of the CBS2 domain in the chloride channel proteins from different species.
See this image and copyright information in PMC

References

    1. Adzhubei I.A., Schmidt S., Peshkin L. A method and server for predicting damaging missense mutations. Nat. Methods. 2010;7:248–249. - PMC - PubMed
    1. Bartter F.C., Pronove P., Gill J.R., MacCardle R.C., Diller E. Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis: a new syndrome. Am. J. Med. 1962;33:811–828. - PubMed
    1. Bianchetti M.G., Bettinelli A., Oetliker O.H., Sereni F. Calciuria in Bartter's and similar syndromes. Clin. Nephrol. 1992;38(6):338. - PubMed
    1. Colussi G., Bettinelli A., Tedeschi S. A thiazide test for the diagnosis of renal tubular hypokalemic disorders. Clin. J. Am. Soc. Nephrol. 2007;2(3):454–460. - PubMed
    1. Favero M., Calo L.A., Schiavon F., Punzi L. Bartter's and Gitelman's disease. Best Pract. Res. Clin. Rheumatol. 2011;25:637–648. - PubMed

LinkOut - more resources