Mutations in the chloride channel gene CLCNKB as a cause of classic Bartter syndrome
| Autor: | Nikola Jeck, Alicia Lakings, Delphine Feldmann, Friedhelm Hildebrandt, Nine V A M Knoers, Lisa M. Guay-Woodford, Henny H. Lemmink, Georges Deschênes, Rainer G. Ruf, Hannsjörg W. Seyberth, Martin Konrad, Lambertus P. W. J. Van Den Heuvel, Rosa Vargas-Poussou, Corinne Antignac, Martin Vollmer |
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| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_specialty
Identificatie van de gen defecten in Bartter syndroom en Gitelman syndroom Anion Transport Proteins DNA Mutational Analysis Molecular Sequence Data Mutation Missense Bartter syndrome Hypocalciuria Identification of the gene defects in Bartter syndrome and Gitelman syndrome Aangeboren stoornissen in magnesiumtransport. Genetica en Pathophysiologie Chloride Channels Internal medicine medicine Humans Missense mutation Amino Acid Sequence Crossing Over Genetic CLCNKB Polymorphism Genetic Base Sequence biology business.industry Bartter Syndrome Membrane Proteins General Medicine Gitelman syndrome medicine.disease Pedigree Phenotype Endocrinology Haplotypes Nephrology Mutation Chloride channel biology.protein ROMK medicine.symptom Nephrocalcinosis Heriditary disorders of magnesiumtransport. Genetic localisation and pathophysiology business Gene Deletion |
| Zdroj: | Journal of the American Society of Nephrology, 11, 8, pp. 1449-1459 CIÊNCIAVITAE Journal of the American Society of Nephrology, 11, 1449-1459 Europe PubMed Central |
| ISSN: | 1046-6673 |
| Popis: | Inherited hypokalemic renal tubulopathies are differentiated into at least three clinical subtypes: (1) the Gitelman variant of Bartter syndrome (GS); (2) hyperprostaglandin E syndrome, the antenatal variant of Bartter syndrome (HPS/aBS); and (3) the classic Bartter syndrome (cBS). Hypokalemic metabolic alkalosis and renal salt wasting are the common characteristics of all three subtypes. Hypocalciuria and hypomagnesemia are specific clinical features of Gitelman syndrome, while HPS/aBS is a life-threatening disorder of the newborn with polyhydramnios, premature delivery, hyposthenuria, and nephrocalcinosis. The Gitelman variant is uniformly caused by mutations in the gene for the thiazide-sensitive NaCl-cotransporter NCCT (SLC12A3) of the distal tubule, while HPS/aBS is caused by mutations in the gene for either the furosemide-sensitive NaK-2Cl-cotransporter NKCC2 (SLC12A1) or the inwardly rectifying potassium channel ROMK (KCNJ1). Recently, mutations in a basolateral chloride channel CLC-Kb (CLCNKB) have been described in a subset of patients with a Bartter-like phenotype typically lacking nephrocalcinosis. In this study, the screening for CLCNKB mutations showed 20 different mutations in the affected children from 30 families. The clinical characterization revealed a highly variable phenotype ranging from episodes of severe volume depletion and hypokalemia during the neonatal period to almost asymptomatic patients diagnosed during adolescence. This study adds 16 novel mutations to the nine already described, providing further evidence that mutations in the gene for the basolateral chloride channel CLC-Kb are the molecular basis of classic Bartter syndrome. Interestingly, the phenotype elicited by CLCNKB mutations occasionally includes HPS/aBS, as well as a Gitelman-like phenotype. |
| Databáze: | OpenAIRE |
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