title: A novel mutation of CLCNKB in a Japanese patient of Gitelman-like phenotype with diuretic insensitivity to thiazide administration.
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.
authors.affiliation: Department of Laboratory Medicine, Faculty of Medicine, Fukuoka University, Japan ; Department of Clinical Laboratory, Fukuoka University Hospital, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ohkubo
authors.affiliation: Department of Clinical Laboratory, Fukuoka University Hospital, Japan.
authors.forename: Tomoe
authors.initials: T
authors.lastname: Matsuzaki
authors.affiliation: Department of Clinical Laboratory, Fukuoka University Hospital, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Yuki
authors.affiliation: Department of Endocrinology and Diabetes, Faculty of Medicine, Fukuoka University, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yoshida
authors.affiliation: Department of Endocrinology and Diabetes, Faculty of Medicine, Fukuoka University, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Terawaki
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Maeyama
authors.affiliation: Department of Clinical Laboratory, Fukuoka University Hospital, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Kawashima
authors.affiliation: Diabetes Center, Karindoh Hospital, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Ono
authors.affiliation: Department of Endocrinology and Diabetes, Faculty of Medicine, Fukuoka University, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yanase
authors.affiliation: Department of Laboratory Medicine, Faculty of Medicine, Fukuoka University, Japan ; Department of Clinical Laboratory, Fukuoka University Hospital, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Matsunaga
keywords: Bartter syndrome type III; CLCNKB; Chondrocalcinosis; ClC-Kb; Gitelman syndrome; Hydrochlorothiazide