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.