A novel initial codon mutation of the thiazide-sensitive Na-Cl cotransporter gene in a Japanese patient with Gitelman's syndrome.
We here report a novel mutation of the thiazide-sensitive Na-Cl cotransporter (TSC) (SLC12A3) gene in a Japanese patient with Gitelman's syndrome (GS). GS is characterized by a renal disorder and is associated with hypokalemia, hypomagnesemia, metabolic alkalosis and hypocalciuria arising from the defective tubular reabsorption of magnesium and potassium. This disease is reportedly caused by mutations in the TSC gene. A 52-year-old man was referred to our hospital because of sleeplessness and tinnitus. He exhibited hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis and hyperreninemic hyperaldosteronism. A renal clearance study revealed that the administration of furosemide decreased chloride reabsorption; however, the ingestion of thiazide failed to decrease chloride reabsorption. A diagnosis of GS was made based on the clinical features, laboratory data and renal function test results. Sequencing of the patient's genomic DNA revealed an A to T transition at the initial codon of exon 1 of the TSC gene (c1A>T). Knowledge of this novel mutation may be helpful for understanding the pathophysiology of GS and the function of TSC as well as for providing genetic counseling.
Aoki
Kazutaka
K
Department of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Tajima
Toshihiro
T
Yabushita
Yasuhiro
Y
Nakamura
Akinobu
A
Nezu
Uru
U
Takahashi
Mayumi
M
Kimura
Mari
M
Terauchi
Yasuo
Y
D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D018387:Codon, Initiator / Q000235:genetics*; D004252:DNA Mutational Analysis; D053579:Gitelman Syndrome / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011955:Receptors, Drug / Q000235:genetics*; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters / Q000235:genetics*
D018387:Codon, Initiator; D011955:Receptors, Drug; C578874:SLC12A3 protein, human; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters