gitelman 's syndrome ( gs ) is the most common inherited renal tubular disorder1 ) . gs results from the defect of na - cl cotransporter ( ncc ) on distal convoluted tubules . it has a long asymptomatic period and often discovered incidentally after adolescence compared to bartter 's syndrome . the cause of the defect of ncc is the mutation on the slc12a3 gene , and it has been reported in more than 400 gs - related mutations . herein , we report on a case of gs , diagnosed by renal biopsy and genetic analysis which present missense mutation in nucleotide 179 , cytosine to threonine ( c.179c > t ) in exon 1 of slc12a3 ) . a 42-year - old man presenting an anterior chest pain , visited the emergency room . according to his medical history , although he visited the hospital with a chest pain repeatedly , heart work up , like electrocardiography and cardiac muscle enzymes , showed non - specific findings and a trans - thoracic echocardiogram revealed normal heart function . the results of the blood test showed : sodium 140meq / l , potassium 2.7meq / l , chloride 91meq / l , total calcium 9.3mg / dl ( 9.5 - 10.9 ) , ionized calcium 2.09mmol / l(2.3 - 2.58 ) , magnesium 1.1mg / dl ( 1.9 - 2.5 ) , ionized magnesium 0.26mmol / l ( 0.45 - 0.6 ) and trans - tubular potasium gradient ( ttkg ) 12.68 . arterial blood gas analysis showed : ph 7.459 , pco2 42.4mmhg , po2 88.5mmhg , hco3 the results of urinalysis showed : sodium 80meq / l , potassium 28.2meq / l , chloride 148meq / l , calcium 2.3mg / dl , creatinine 21.7mg / dl , spot urine ca / cr 0.1 , and 24 hours urine magnesium 21.0meq / l / day ( 5 - 17 ) . chest x - ray and kidney ultrasonography showed nonpathognomonic findings . to evaluate for hypokalemia , which persists over 10 years combined with other electrolyte imbalances , we took an ultrasonography guided kidney biopsy . there were 3 global sclerosises among 51 glomeruli , and the light microscopy finding was normal without minimal increase of mesangial cell proliferation . immunofluorescence findings showed all negativity for igg , iga , igm , c3 , c4 , c1q , and lambda in the glomerulus . the result of the immunohistochemistry of ncc on tubules , and the expression degree was decreased compared with the control ( fig . although his family ( parents and 3 sisters ) did not show any clinical abnormality or electrolyte imbalances , we analyzed genomic dna of the patient and his family in keimyung university medical genetics institute . genomic dna was isolated from peripheral blood by using the wizard genomic dna purification kit according to the manufacture 's instruction ( promega , madison , wi , usa ) . amplification of the coding sequence of the slc12a3 gene by polymerase chain reaction was carried out as previously described . polymerase chain reaction - single strand conformational polymorphism ( pcr - sscp ) was performed . pcr products in the patient , his family , and normal control were electrophoresed through 10% polyacrylamide gels . the result in patient , a double mutant band was found , his family had only one band ( fig . 2 ) . to get apparent result of sequencing , pcr products were cloned by topota cloning ( invitrogen ltd . , paisley , united kingdom ) and direct sequencing was performed on those pcr products that showed altered band mobility in the above analysis . variations in the sequences between gs and matched normal sample were performed using the abi 3730 dna sequencer ( bionics inc , korea ) . the result revealed that the patient had homozygous missense mutation of nucleotide 179 , cytosine to threonine ( acg to atg ) on exon 1 of the slc12a3 gene . his family has heterozygous mutation at the same region , and supports the diagnosis of gs and carrier ( figs . 3 , 4 ) . hypokalemia is a common finding in overall patients , furthermore it occurs in more than 20% of hospitalized patients4 ) . the kidney is a key regulator that controls the homeostasis of potassium , 80% of potassium transit the kidney . therefore , it needs to be considered about renal tubular dysfunction in patients with hypokalemia . especially , if adult patients who have other electrolyte imbalance , like hypomagnesemia and hypocalciuria , in addition to hypokalemia , come to the hospital . we have to distinguish gs from bartter 's syndrome . it is a thiazide - like salt - losing tubulopathy which shows familial hypokalemic and hypochloremic metabolic alkalosis5 ) . it has developed by a mutation of slc12a3 gene that encodes thiazide - sensitive ncc on distal convoluted tubule . gs related slc12a3 mutations have been reported to have more than 400 different forms , from missense mutation to gross deletion and insertion mutation3 ) . we report a case of homozygous missense mutation in c.179c > t on exon 1 that leads transposition of codon 60 , threonine to methionine . the c.179c > t mutation has been commonly detected in asia including japan and china6789 ) . this is the first report which analyzes pedigree with c.179c > t mutation in korea . a carrier state of slc12a3 gene mutation was reported in 1% of the general population . although gs is the most common inherited tubular disorder , it was not commonly diagnosed in the clinical field1 ) . the clinical manifestation of gs is diverse from being symptomless to tetany , growth retardation and fatal cardiac arrhythmia . this case was diagnosed by an attentive inspection of the electrolyte imbalance , even though the symptom was not specific . after being diagnosed as gs , he took oral magnesium and potassium and he did not complain about the chest discomfort and weakness anymore . actually , homozygous mutations in slc12a3 gene are only reported in 18% of patients while heterozygous mutations are more frequently observed1011 ) . but , the type and character of the mutation does not clearly correlate with the symptoms12 ) . their values of electrolytes , such as sodium , potassium , and chloride were normal and they did not complain of any symptoms . although we did not evaluate other serum and urine electrolytes , and chemistry of the family , they need to be evaluated even if they experience nonspecific symptoms . knowledge about the accurate location and pattern of the gene mutation can lead us to better understand the function of slc12a3 gene and the disease entity of gs . if physicians suspect gs , they have to do a genetic analysis which is a gold standard tool for diagnosing gs . and , this positive attitude leads to early detection and improves the quality of life of the patient with gs presenting non - specific symptom like as fatigue , thirst , dizziness , general weakness .
a 42-year - old man came to the hospital presenting chest discomfort and general weakness . 
 he had come to the hospital with the same symptoms 3 months ago and 12 years prior . 
 his laboratory test showed hypokalemia , hypomagnesemia and hypocalciuria . 
 the arterial blood gas analysis showed hypochloremic metabolic alkalosis . 
 he had an ultrasonography guided renal biopsy , the result was normal at light microscopy and immunofluorescence microscopy . 
 however , a special stain for na - cl cotransporter was weakly expressed compared with the control . 
 the patient and his family underwent genetic sequencing about the slc12a3 gene . 
 he had a homozygous mutation in the 179th nucleotide of exon 1 on the slc12a3 gene ( p.thr60met ) and his parents and sisters were diagnosed as carrier state of gitelman 's syndrome ( gs ) . 
 gs is an inherited tubular disorder which presents mild hypokalemia , hypomagnesemia and hypocalciuria . 
 since the symptoms and laboratory results are not severe , it can go unnoticed by physicians . 
 herein we present a family with gs , diagnosed by genetic sequencing .