title: Phenotype and genotype analysis in Chinese patients with Gitelman's syndrome.
abstract: Inactivation mutations of the luminal thiazide-sensitive NaCl cotransporter (NCC) in the distal convoluted tubules or the basolateral chloride channel (CLCNKB) in the distal nephron are the most common genetic mutations in Gitelman's syndrome (GS) or Bartter's syndrome (BS). We conducted clinical and molecular studies in Chinese patients with GS or BS. Twenty patients with chronic hypokalemia (15 males and five females, age 25 +/- 7 yr) from 15 unrelated Chinese families were investigated. All had renal K+ wasting, metabolic alkalosis, and normotension. The urinary calcium excretion rate was used to distinguish between BS or GS on clinical grounds. Clinical symptoms and biochemical studies were recorded. Molecular analysis included PCR single-strand confirmational polymorphism, direct sequencing of both the NCC and CLCNKB genes, and restriction fragment length polymorphism. Sixteen patients had a clinical diagnosis of GS with hypocalciuria and four BS without hypocalciuria. Four of these 20 patients did not have hypomagnesemia. The males had severe hypokalemia [1.9 +/- 0.4 mEq/liter (mmol/liter)] with paralytic episodes, whereas females had moderate hypokalemia [2.6 +/- 0.2 mEq/liter (mmol/liter)] and less severe symptoms. There were no mutations detected in CLCNKB. Twelve NCC mutations, including six novel mutations and nine recurrent ones, were identified. Allele frequency of the detected NCC mutations was 3% in 100 healthy subjects. Some GS patients with NCC mutations may have normocalciuria and/or normomagnesemia. Gender differences may account for phenotype variability. Screening of these identified NCC mutations remains the gold standard for the diagnosis of GS.
authors.affiliation: Division of Nephrology, Department of Medicine, Tri-Service General Hospital, Number 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan. shihhualin@yahoo.com
authors.forename: Shih-Hua
authors.initials: SH
authors.lastname: Lin
authors.forename: Jen-Chuan
authors.initials: JC
authors.lastname: Shiang
authors.forename: Che-Chung
authors.initials: CC
authors.lastname: Huang
authors.forename: Sung-Sen
authors.initials: SS
authors.lastname: Yang
authors.forename: Yu-Juei
authors.initials: YJ
authors.lastname: Hsu
authors.forename: Chih-Jen
authors.initials: CJ
authors.lastname: Cheng
mesh_terms: D000293:Adolescent; D000328:Adult; D000471:Alkalosis / Q000235:genetics* / Q000503:physiopathology; D027321:Anion Transport Proteins / Q000235:genetics*; D002118:Calcium / Q000652:urine*; D018118:Chloride Channels / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007008:Hypokalemia / Q000235:genetics* / Q000503:physiopathology; D007668:Kidney / Q000503:physiopathology; D008275:Magnesium Deficiency / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D010641:Phenotype; D012727:Sex Characteristics; D049992:Sodium Chloride Symporters; D027981:Symporters / Q000235:genetics*; D013577:Syndrome
chemical_list: D027321:Anion Transport Proteins; C412733:CLCNKB protein, human; D018118:Chloride Channels; D008565:Membrane Proteins; D049992:Sodium Chloride Symporters; D027981:Symporters; D002118:Calcium