• Gitelman syndrome
• Refractory hypomagnesemia
• case report
• metabolic alkalosis
• recurrent hypokalemia

• Humans
• Gitelman Syndrome/diagnosis
• Gitelman Syndrome/complications
• Male
• Hypokalemia/etiology
• Hypokalemia/diagnosis
• Child
• Solute Carrier Family 12, Member 3
• Failure to Thrive/etiology
• Failure to Thrive/diagnosis
• Mutation
• Alkalosis/etiology
• Alkalosis/diagnosis
• Magnesium Deficiency/diagnosis
• Magnesium Deficiency/complications
• Recurrence
• Magnesium/blood
• Electrocardiography

• SLC12A3
• Genetic variant
• Gitelman syndrome
• Hypokalemia
• Metabolic alkalosis

• Humans
• Gitelman Syndrome/genetics
• Gitelman Syndrome/diagnosis
• Solute Carrier Family 12, Member 3/genetics
• Child
• Male
• Retrospective Studies
• Female
• Adolescent
• Genetic Association Studies
• Phenotype
• Republic of Korea
• Child, Preschool
• Mutation
• Potassium/blood
• Genetic Predisposition to Disease
• Chlorides/blood

• 2020R1A2C1100974 Ministry of Science and ICT, South Korea

• Gitelman syndrome
• Na+-Cl− cotransporter
• SLC12A3
• cation-Cl− cotransporter
• distal tubule

• Humans
• Animals
• Homeostasis/physiology
• Solute Carrier Family 12, Member 3/metabolism
• Water-Electrolyte Balance/physiology
• Sodium/metabolism
• Kidney/metabolism

• Canadian Institutes of Health and Research
• Kidney Foundation of Canada (KFOC)

• human genetics
• magnesium
• homeostasis

• Humans
• Magnesium/metabolism
• Homeostasis
• Animals
• Intestinal Absorption
• Mice
• Renal Reabsorption

• Gitelman syndrome
• SLC12A3 gene
• clinical characteristics
• gene mutation
• whole-exome sequencing

• Zhejiang Provincial Government Scholarship

• SLC12A3
• Gitelman syndrome
• exon splicing
• exonic variant
• minigene assay

• bartter syndrome
• cardiac arrythmia
• familial hypokalemia-hypomagnesemia
• gitelman syndrome
• implantable cardioverter-defibrillator (icd)
• metabolic alkalosis

• Gitelman syndrome
• Slc12a3
• compound heterozygous
• hypokalemia
• mouse model

• Humans
• Gitelman Syndrome/genetics
• Mutation
• Solute Carrier Family 12, Member 3/genetics

Gitelman syndrome (GS) is an autosomal recessive salt-losing renal tubulopathy arising from mutations in the thiazide-sensitive Na-Cl cotransporter gene. Due to its low incidence and lack of awareness, GS can be easily misdiagnosed or missed in diagnosis.

A 24-year-old male presented with > 4 years of repeated limb weakness without any treatment. The previous day, the patient was bitten by ants and showed weakness of the lower limbs. The patient had hypokalemia (1.66-2.83 mmol/L), hypomagnesemia (0.4 mmol/L), hypocalciuria (1.51-2.46 mmol/d), metabolic alkalosis (7.47-7.54), normal blood pressure, and increased activity of aldosterone and plasma renin activity (PRA) (PRA 6.4 and 16.45 ng/mL/h and aldosterone 330.64 and 756.82 pg/mL in the supine and upright position, respectively). In addition, SLCI2A3 gene mutation with GS was diagnosed. Oral and intravenous supplementation with potassium and magnesium was initiated. Serum magnesium returned to 0.48 mmol/L and serum potassium returned to 3.08 mmol/L, alleviating the patient’s fatigue symptoms.

GS should be considered in patients with hypokalemia complicated with hypomagnesemia. Genetic testing is essential to confirm the diagnosis.

• Gitelman syndrome
• Limb weakness
• Hypokalemia
• Hypomagnesemia
• Hypocalciuria
• Genetic testing
• Case report

• 22Na+ uptake activity
• Gitelman syndrome
• SLC12A3 gene
• Thiazide test
• frequent mutations

Recurrent mutations in the SLC12A3 gene responsible for autosomal recessive Gitelman syndrome (GS) are frequently reported, but the exact prevalence is unknown. The rapid detection of recurrent SLC12A3 mutations may help in the early diagnosis of GS. This study was aimed to investigate the prevalence of recurrent SLC12A3 mutations in a Taiwan cohort of GS families and develop a simple and rapid method to detect recurrent SLC12A3 mutations. One hundred and thirty independent Taiwan families with genetically confirmed GS were consecutively enrolled to define recurrent SLC12A3 mutations and determine their prevalence. Using TaqMan probe-based real-time polymerase chain reaction, we designed a mutation detection plate with all recurrent mutations. We validated this mutation detection plate and tested its feasibility in newly diagnosed GS patients. A total of 57 mutations in the SLC12A3 gene were identified and 22 including 2 deep intronic mutations were recurrent mutations consisting of 87.1% (242/278, 18 triple) of all allelic mutations. The recurrent mutation-based TaqMan assays were fully validated with excellent sensitivity and specificity in genetically diagnosed GS patients and healthy subjects. In clinical validation, recurrent mutations were recognized in 92.0% of allelic mutations from 12 GS patients within 4 h and all were confirmed by direct sequencing. Recurrent SLC12A3 mutations are very common in Taiwan GS patients and can be rapidly identified by this recurrent mutation-based SLC12A3 mutation plate.

• Gitelman syndrome
• hypokalemia
• kidney transplantation
• the SLC12A3 gene

• Adult
• Female
• Gitelman Syndrome/genetics
• Humans
• Kidney
• Mutation
• Solute Carrier Family 12, Member 3/genetics
• Tissue and Organ Harvesting

• fluid electrolyte and acid-base disturbances
• pregnancy

Genetic testing of patients with inherited kidney diseases has emerged as a tool of clinical utility by improving the patients’ diagnosis, prognosis, surveillance and therapy.

The present study applied a Next Generation Sequencing (NGS)-based panel, named NephroPlex, testing 115 genes causing renal diseases, to 119 individuals, including 107 probands and 12 relatives. Thirty-five (poly)cystic and 72 non (poly)cystic individuals were enrolled. The latter subgroup of patients included Bardet-Biedl syndrome (BBS) patients, as major components.

Disease-causing mutations were identified in 51.5 and 40% of polycystic and non-polycystic individuals, respectively. Autosomal dominant polycystic kidney disease (ADPKD) patients with truncating PKD1 variants showed a trend towards a greater slope of the age-estimated glomerular filtration rate (eGFR) regression line than patients with (i) missense variants, (ii) any PKD2 mutations and (iii) no detected mutations, according to previous findings. The analysis of BBS individuals showed a similar frequency of BBS4,9,10 and 12 mutations. Of note, all BBS4-mutated patients harbored the novel c.332+1G>GTT variant, which was absent in public databases, however, in our internal database, an additional heterozygote carrier was found. All BBS4-mutated individuals originated from the same geographical area encompassing the coastal provinces of Naples.

In conclusion, these findings indicate the potential for a genetic panel to provide useful information at both clinical and epidemiological levels.

The online version contains supplementary material available at 10.1007/s40620-021-01048-4.

• ADPKD
• Bardet-Biedl syndrome
• Gene-panel
• Inherited kidney disease
• NGS

• ATP, adenosine triphosphate
• Blood pressure regulation
• CCC, cation-coupled chloride cotransporters
• CCT, conserved carboxy-terminal
• CNI, calcineurin inhibitors
• CUL3, cullin 3
• CUL3/KLHL3-WNK-SPAK/OSR1
• Ca2+, calcium ion
• Cardiovascular disease
• DAG, diacylglycerol
• DCT, distal convoluted tubule
• DUSP, dual specificity phosphatases
• ECF, extracellular fluid
• ELISA, enzyme-bound immunosorbent analysis
• ERK, extracellular signal-regulated kinases
• EnaC, epithelial sodium channels
• GABA, gamma-aminobutyric acid
• HEK293, human embryonic kidney 293
• Hypertension
• I1, inhibitor 1
• K+, potassium ion
• KCC, potassium-chloride-cotransporters
• KLHL3, kelch-like 3
• KS-WNK1, kidney specific-WNK1
• Kinase inhibitors
• MAPK, mitogen-activated protein kinase
• MO25, mouse protein-25
• Membrane trafficking
• NCC, sodium–chloride cotransporters
• NKCC, sodium–potassium–chloride-cotransporter
• Na+, sodium ion
• NaCl, sodium chloride
• NaCl-cotransporter NCC
• OSR1, oxidative stress-responsive gene 1
• PCT, proximal convoluted tubule
• PHAII, pseudohypoaldosteronism type II
• PP, protein phosphatase
• PV, parvalbumin
• ROMK, renal outer medullary potassium
• RasGRP1, RAS guanyl-releasing protein 1
• SLC12, solute carrier 12
• SPAK, Ste20-related proline-alanine-rich-kinase
• TAL, thick ascending limb
• Therapeutic targets
• WNK, with-no-lysine kinases
• mDCT, mammalian DCT
• mRNA, messenger RNA

Gitelman syndrome (GS) and Bartter syndrome (BS) type III are both rare, recessively inherited salt-losing tubulopathies caused by SLC12A3 and CLCNKB mutations, respectively. We described a 48-year-old male patient with fatigue, carpopedal spasm, arthralgia, hypokalemic alkalosis, mild renal dysfunction, hypomagnesemia, hypocalciuria, hyperuricemia, normotension, hyperreninemia and chondrocalcinosis in knees and Achilles tendons. His parents are first cousin. Genetic analysis revealed simultaneous homozygous mutations in SLC12A3 gene with c.248G>A, p.Arg83Gln and CLCNKB gene with c.1171T>C, p.Trp391Arg. The second younger brother of the proband harbored the same simultaneous mutations in SLC12A3 and CLCNKB and exhibited similar clinical features except normomagnesemia and bilateral kidney stones. The first younger brother of the proband harbored the same homozygous mutations in CLCNKB and exhibited clinical features of hypokalemia, normomagnesemia, hypercalciuria and hyperuricemia. Potassium chloride, spironolactone and potassium magnesium aspartate were prescribed to the proband to correct electrolytic disturbances. Benzbromarone and febuxostat were prescribed to correct hyperuricemia. The dose of potassium magnesium aspartate was subsequently increased to alleviate arthralgia resulting from calcium pyrophosphate deposition disease (CPPD). To the best of our knowledge, we are the first to report an exceptionally rare case in an inbred Chinese pedigree with simultaneous homozygous mutations in SLC12A3 and CLCNKB. GS and BS type III have significant intrafamilial phenotype heterogeneity. When arthralgia is developed in patients with GS and BS, gout and CPPD should both be considered.

• Bartter syndrome
• CLCNKB
• Gitelman syndrome
• SLC12A3
• calcium pyrophosphate deposition disease
• gout

• Endoplasmic reticulum stress
• Gitelman syndrome
• SLC12A3 gene mutation

• Adult
• Endoplasmic Reticulum Stress
• Female
• Gitelman Syndrome/etiology
• Gitelman Syndrome/metabolism
• Gitelman Syndrome/pathology
• Homozygote
• Humans
• Male
• Mutation, Missense
• Pedigree
• Prognosis
• Solute Carrier Family 12, Member 3/genetics

• Gitelman syndrome
• genetic renal disease
• heterozygosity
• potassium
• whole-exome sequencing

• Gitelman's syndrome
• congenital tubulopathy
• genotype
• mutation-genetics
• phenotype [mesh]

Gitelman syndrome is a rare salt-losing renal tubular disorder associated with mutation of SLC12A3 gene, which encodes the Na-Cl co-transporter (NCCT). Gitelman syndrome is characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria, and renin-angiotensin-aldosterone system (RAAS) activation. Different SLC12A3 variants may lead to phenotypic variability and severity.

In this study, we reported the clinical features and genetic analysis of a Chinese pedigree diagnosed with Gitelman syndrome.

The proband exhibited hypokalaemia, hypomagnesemia, metabolic alkalosis, but hypercalciuria and kidney stone formation. The increased urinary calcium excretion made it confused to Bartter syndrome. The persistent renal potassium wasting resulted in renal tubular lesions, and might affect urinary calcium reabsorption and excretion. Genetic analysis revealed mutations of SLC12A3 gene with c.433C > T (p.Arg145Cys), c.1077C > G (p.Asn359Lys), and c.1666C > T (p.Pro556Ser). Potential alterations of structure and function of NCCT protein due to those genetic variations of SLC12A3 are predicted. Interestingly, one sibling of the proband carried the same mutant sites and exhibited similar clinical features with milder phenotypes of hypokalemia and hypomagnesemia, but hypocalciuria rather than hypercalciuria. Family members with at least one wild type copy of SLC12A3 had normal biochemistry. With administration of spironolactone, potassium chloride and magnesium supplement, the serum potassium and magnesium were maintained within normal ranges.

In this study, we identified compound mutations of SLC12A3 associated with varieties of clinical features. Further efforts are needed to investigate the diversity in clinical manifestations of Gitelman syndrome and its correlation with specific SLC12A3 mutations.

• Gitelman syndrome
• Hypercalciuria
• Hypokalemia
• SLC12A3

Renal tubular cells release urinary extracellular vesicles (uEV) that are considered a promising source of molecular markers for renal dysfunction and injury. We investigated uEV proteomes of patients with hereditary salt-losing tubulopathies (SLTs), focusing on those caused by Gitelman and Bartter (BS) syndromes, to provide potential markers for differential diagnosis. Second morning urine was collected from patients with genetically proven SLTs and uEV were isolated by the ultracentrifugation-based protocol. The uEV proteome was run through a diagonal bidimensional electrophoresis (16BAC/SDS-PAGE), to improve hydrophobic protein resolution. Sixteen differential spots from the proteome of two variants (BS2 and BS3) were analysed by nLC-ESI-MS/MS after in-gel tryptic digestion. A total of 167 protein species were identified from 7 BS2 spots and 9 BS3 spot. Most of these proteins were membrane-associated proteins, in particular transmembrane proteins, and were related to typical renal functions. The differential content of some uEV was then validated by immunoblotting. Our work suggests that uEV proteomics represents a promising strategy for the identification of differential SLT proteins. This could play a role in understanding the pathophysiological disease mechanisms and may support the recognition of different syndromes.

• Bartter syndrome
• Gitelman syndrome
• diagonal electrophoresis
• exosomes
• extracellular vesicles

• Randall’s plaque
• extracellular vesicles
• monocyte chemoattractant protein-1
• nephrolithiasis
• neutrophil gelatinase-associated lipocalin
• urinary stone disease

Thiazide diuretic (TZD)-mediated chronic reduction of arterial pressure is thought to occur through decreased total peripheral vascular resistance. Further, the decreased peripheral vascular resistance is accomplished through TZD activation of an extrarenal target, resulting in inhibition of vascular constriction. However, despite greater than five decades of investigation, little progress has been made into the identification of the TZD extrarenal target. Proposed mechanisms range from direct inhibition of constrictor and activation of relaxant signaling pathways in the vascular smooth muscle to indirect inhibition through decreased neurogenic and hormonal regulatory pathways. Surprisingly, particularly in view of this lack of progress, comprehensive reviews of the subject are absent. Moreover, even though it is well recognized that 1) several types of hypertension are insensitive to TZD reduction of arterial pressure and, further, TZD fail to reduce arterial pressure in normotensive subjects and animals, and 2) different mechanisms underlie acute and chronic TZD, findings derived from these models and parameters remain largely undifferentiated. This review 1) comprehensively describes findings associated with TZD reduction of arterial pressure; 2) differentiates between observations in TZD-sensitive and TZD-insensitive hypertension, normotensive subjects/animals, and acute and chronic effects of TZD; 3) critically evaluates proposed TZD extrarenal targets; 4) proposes guiding parameters for relevant investigations into extrarenal TZD target identification; and 5) proposes a working model for TZD chronic reduction of arterial pressure through vascular dilation.

• arterial blood pressure
• diuresis
• extrarenal
• hypertension
• plasma volume
• renal
• thiazide diuretics
• vasoconstriction

Licorice-induced severe hypokalemic rhabdomyolysis is clinically rare. Gitelman syndrome (GS) is the most common inherited renal tubular disease, while diabetes is one of the most prevalent diseases in the world. Recently, some studies have found that GS patients had higher diabetic morbidity. However, the coexistence of these three diseases has yet to be reported.

We report the case of a 62-year-old Chinese man who was admitted with weakness in the extremities, muscle pain, and dark-colored urine. He had consumed liquorice water daily for seven days prior to admission. The laboratory tests revealed a serum potassium level of 1.84 mmol/L, magnesium 0.68 mmol/L, creatinine phosphokinase (CK) 10117 IU/L, and marked hemoglobinuria. Fractional chloride excretion and fractional magnesium excretion were increased. Plasma renin activity and aldosterone concentration were within the normal ranges. Sequence analysis of the SLC12A3 gene revealed that he had compound heterozygous mutations. The diagnosis of liquorice-induced severe hypokalemic rhabdomyolysis with GS and diabetes was thus genetically confirmed. Serum potassium and CK quickly improved with potassium replacement therapy, hydration, and discontinuation of liquorice ingestion. Upon follow-up at 3 mo, the levels of CK, myoglobin, and potassium remained normal, and magnesium was above 0.6 mmol/L.

This case emphasizes that liquorice consumption and GS should be considered causes of hypokalemia and that the diabetic status of GS patients should be noted in the clinic.

• Hypokalemia
• Rhabdomyolysis
• Liquorice
• Gitelman syndrome
• Diabetes
• Case report

• Arterial hypertension
• Gitelman syndrome
• NaCl cotransporter
• Structure-function
• Thiazides
• WNKs
• sNCC

• Diagnosis
• Gitelman syndrome
• gene analysis
• hypertension
• hypokalaemia

• Gitelman Syndrome/diagnosis
• Gitelman Syndrome/genetics
• Humans
• Hypertension/etiology
• Hypertension/genetics
• Hypocalcemia/etiology
• Hypokalemia/etiology
• Hypokalemia/genetics
• Male
• Middle Aged
• Mutation
• Solute Carrier Family 12, Member 3/genetics

Gitelman syndrome (GS) is an autosomal recessive disorder caused by genic mutations of SLC12A3 (Solute carrier family 12 member 3), which encodes the Na-Cl cotransporter (NCC), and presents with characteristic metabolic abnormalities, including hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria. In this study, we report a case of a GS pedigree, including analysis of GS-associated gene mutations.

We performed next-generation sequencing analysis and Sanger sequencing to explore the SLC12A3 mutations in a GS pedigree that included a 35-year-old female patient with GS and five family members within three generations. Furthermore, we summarized their clinical manifestations and analyzed laboratory parameters related to GS.

The female proband (the patient with GS) presented with intermittent fatigue and transient periods of tetany, along with significant hypokalemia, hypomagnesemia, and hypocalciuria. All other members of the pedigree had normal laboratory results without obvious GS-related symptoms. Genetic analysis of the SLC12A3 gene identified two novel missense mutations (c.1919A > G, p.N640S in exon 15; c.2522A > G, p.D841G in exon 21) in the patient with GS. Moreover, we demonstrated that her mother, younger maternal uncle, and cousin were carriers of one mutation (c.1919A > G), and her father was the carrier of the other (c.2522A > G).

This is the first report of these two novel pathogenic variants of SLC12A3 and their contribution to GS. Further functional studies are particularly warranted to explore the underlying molecular mechanisms.

The online version of this article (10.1186/s12881-018-0527-7) contains supplementary material, which is available to authorized users.

• Compound heterozygous
• Gitelman syndrome
• Pedigree
• SLC12A3

• SLC12A3
• hypokalemic metabolic alkalosis
• hypomagnesemia
• salt-losing tubulopathy
• thiazide-sensitive sodium-chloride cotransporter

• CPPD
• Magnesium
• calcium pyrophosphate deposition disease
• chondrocalcinosis
• hypomagnesemia
• pseudogout

In rare cases, patients with Gitelman syndrome may present with hypokalemic paralysis mimicking Guillain–Barré syndrome. The severity of resultant symptoms may be life‐threatening. Controversial drugs such as aldactone, amiloride, and eplerenone should be used in this situation despite the lack of safety data.

• Controversial drugs
• Gitelman syndrome
• Guillain–Barré syndrome
• hypokalemic paralysis
• outcome
• pregnancy

Gitelman syndrome is an autosomal recessive disease mostly associated with loss‐of‐function mutations of the SLC12A3 gene and featured by clinical hypokalemia, hypomagnesemia, hypocalciuria, and histologically hypertrophy of the juxtaglomerular apparatus. A novel homozygous mutation (p.Arg399Pro) at the extracellular domain of SLC12A3 was found and correlated with the severe clinical manifestations.

• Gitelman syndrome
• SLC12A3
• phenotype–genotype relation
• review

Gitelman’s syndrome (GS) is a salt-losing tubulopathy with an autosomal recessive inheritance caused by mutations of SLC12A3, which encodes for the thiazide-sensitive NaCl cotransporter. In this study we report a new mutation of SLC12A3 found in two brothers affected by GS. Hypokalemia, hypocalciuria and hyper-reninemia were present in both patients while hypomagnesemia was detected only in one. Both patients are compound heterozygotes carrying one well known GS associated mutation (c.2581 C > T) and a new one (c.283delC) in SLC12A3 gene. The new mutation results in a possible frame-shift with a premature stop-codon (pGln95ArgfsX19). The parents of the patients, heterozygous carriers of the mutations found in SLC12A3, have no disease associated phenotype. Therefore, the new mutation is causative of GS.

• Gitelman’s syndrome
• Thiazide-sensitive NaCl cotransporter
• Frame-shift mutation
• Tubulopathy
• SLC12A3 gene

Loss of function of mutated solute carrier family 12 member 3 (SLC12A3) gene is the most frequent etiology for Gitelman syndrome (GS), which is mainly manifested by hypokalemia, hypomagnesemia and hypocalciuria. We report the genetic characteristics of one suspicious Chinese GS pedigree by gene sequencing. Complete sequencing analysis of the SLC12A3 gene revealed that both the proband and his elder sister had a novel homozygous SLC12A3 mutation: c.2099T>C and p.Leu700Pro. Moreover, the SLC12A3 genes of his mother and daughter encoded the same mutated heterozygote. It was noted that in this pedigree, only the proband complained about recurrent episodes of bilateral lower limb weakness over 8 years, while his elder sister, mother and daughter did not present symptoms. The inconsistent clinical features of this pedigree implied that besides diverse phenotypes possibly originated from the same genotype, gender difference may also dominate the variant GS phenotypes. Further genetic and proteomic research are needed to investigate the precise mechanisms of GS, including the study of specific ethnicities.

Introduction. Gitelman's syndrome (GS) is an autosomal recessive inherited defect in the thiazide-sensitive sodium-chloride cotransporter (NCCT) in the renal distal convoluted tubule. Physiologic changes of pregnancy promote renal potassium wasting, but serum potassium levels are kept in the physiologic range by increased levels of progesterone, which resist kaliuresis. In the presence of GS, this compensatory mechanism is easily overwhelmed, resulting in profound hypokalemia. We present a case of an 18-year-old primigravida with undiagnosed GS who presented with hyperemesis gravidarum in her 7th week of pregnancy. This report adds to the limited experience with GS in pregnancy as reported in literature and provides additional information on medical management that leads to successful maternal and fetal outcomes.

• Gitelman Syndrome
• Homozygous mutation
• Pedigree
• SLC12A3 gene

• Adult
• Asian People
• Female
• Genetic Testing
• Genotype
• Gitelman Syndrome/genetics
• Homozygote
• Humans
• Male
• Mutation/genetics
• Pedigree
• Phenotype
• Prognosis
• Solute Carrier Family 12, Member 3/genetics

Three phosphorescent cyclometalated iridium(iii) complexes with mitochondria-specific localization and apoptosis-inducing capability have been explored as the theranostic anticancer agents.

• Bartter Syndrome
• CLCNKB
• Gitelman Syndrome
• SLC12A3
• Salt-losing Tubulopathy

• Adolescent
• Adult
• Alleles
• Bartter Syndrome/genetics
• Bartter Syndrome/pathology
• Chloride Channels/genetics
• DNA Mutational Analysis
• Female
• Genetic Association Studies
• Genotype
• Gitelman Syndrome/genetics
• Gitelman Syndrome/pathology
• Humans
• Hypokalemia/etiology
• Male
• Middle Aged
• Phenotype
• Polymorphism, Genetic
• Solute Carrier Family 12, Member 3/genetics
• Young Adult

• Seoul National University Hospital
• Ministry for Health and Welfare

• Female
• Gitelman Syndrome/genetics
• Humans
• Male
• Mutation
• Pedigree
• Solute Carrier Family 12, Member 3/genetics

• Adolescent
• Adult
• Aged
• Child
• Chlorides/urine
• Female
• Genotype
• Gitelman Syndrome/blood
• Gitelman Syndrome/diagnosis
• Gitelman Syndrome/genetics
• Humans
• Hydrochlorothiazide/administration & dosage
• Magnesium/blood
• Magnesium/urine
• Magnesium Deficiency/blood
• Male
• Middle Aged
• Mutation
• ROC Curve
• Sensitivity and Specificity
• Sodium/urine
• Sodium Chloride Symporter Inhibitors/administration & dosage
• Solute Carrier Family 12, Member 3/genetics

• Gitelman's syndrome
• hypertension
• thiazide-sensitive Na+–Cl− cotransporter

• Genotype
• Gitelman Syndrome/genetics
• Humans
• Hypertension/genetics
• Mutation, Missense
• Phenotype
• Polymorphism, Genetic
• Sodium Chloride Symporters/genetics
• Sodium Chloride Symporters/metabolism
• Solute Carrier Family 12, Member 3/genetics
• Solute Carrier Family 12, Member 3/metabolism
• Thiazides/pharmacology