Novel Mutations of the Chloride Channel Kb Gene in Two Japanese Patients Clinically Diagnosed as Bartter Syndrome with Hypocalciuria
| Autor: | Shigeru Fukuyama, Takao Ohta, Mutumi Higa, Misako Hiramatsu, Motohiro Akagi |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty Adolescent Endocrinology Diabetes and Metabolism Anion Transport Proteins Clinical Biochemistry Bartter syndrome Biochemistry Hypocalciuria Endocrinology Tubulopathy Chloride Channels Internal medicine medicine Humans Child CLCNKB Kidney biology urogenital system business.industry Biochemistry (medical) Bartter Syndrome Membrane Proteins Gitelman syndrome medicine.disease Bartter's syndrome medicine.anatomical_structure Mutation biology.protein ROMK Calcium medicine.symptom business |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 89:5847-5850 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jc.2004-0775 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|