title: Novel mutations of the chloride channel Kb gene in two Japanese patients clinically diagnosed as Bartter syndrome with hypocalciuria.
abstract: Hypokalemic metabolic tubulopathy, such as in Bartter syndrome and Gitelman syndrome, is caused by the dysfunction of renal electrolyte transporters. Despite advances in molecular genetics with regard to hypokalemic metabolic tubulopathy, recent reports have suggested that the phenotype-genotype correlation is still confusing, especially in classic Bartter and Gitelman syndromes. We report here two Japanese patients who suffered from clinically diagnosed classic Bartter syndrome but who presented hypocalciuria. Hypocalciuria is generally believed to be a pathognomonic finding of NCCT malfunction. To better understand the genotype-phenotype correlation in these two cases, we screened four renal electrolyte transporter genes [Na-K-2Cl cotransporter (NKCC2), renal outer medullary K channel (ROMK), Cl channel Kb (ClC-Kb), and Na-Cl cotransporter (NCCT)] by the PCR direct sequencing method. We identified three ClC-Kb allelic variants, including two new mutations (L27R and W610X in patient 1 and a G to C substitution of a 3' splice site of intron 2 and W610X in patient 2). We did not find any mutations in the other three genes. Our present data suggest that some ClC-Kb mutations may affect calcium handling in renal tubular cells.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, 903-0125 Japan. tohta@med.u-ryukyu.ac.jp.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Fukuyama
authors.forename: Misako
authors.initials: M
authors.lastname: Hiramatsu
authors.forename: Motohiro
authors.initials: M
authors.lastname: Akagi
authors.forename: Mutumi
authors.initials: M
authors.lastname: Higa
authors.forename: Takao
authors.initials: T
authors.lastname: Ohta
mesh_terms: D000293:Adolescent; D027321:Anion Transport Proteins / Q000235:genetics*; D001477:Bartter Syndrome / Q000235:genetics* / Q000652:urine; D002118:Calcium / Q000652:urine*; D002648:Child; D018118:Chloride Channels / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation
chemical_list: D027321:Anion Transport Proteins; C412733:CLCNKB protein, human; D018118:Chloride Channels; D008565:Membrane Proteins; D002118:Calcium