Molecular pathogenesis of Bartter’s and Gitelman’s syndromes

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Molecular pathogenesis of Bartter’s and Gitelman’s syndromes Ira Kurtz Kidney International Volume 54, Issue 4, Pages 1396-1410 (October 1998) DOI: 10.1046/j.1523-1755.1998.00124.x Copyright © 1998 International Society of Nephrology Terms and Conditions

Figure 1 Two patients with neonatal Bartter’s syndrome described by Landau et al.25 Both patients have the typical facial appearance with prominent forehead, triangular face, drooping mouth, and large eyes and pinnae. Kidney International 1998 54, 1396-1410DOI: (10.1046/j.1523-1755.1998.00124.x) Copyright © 1998 International Society of Nephrology Terms and Conditions

Figure 2 Approach to the clinical differentiation between Bartter’s syndrome and Gitelman’s syndrome based on divalent cation metabolism. Note that some patients with type-3 BS have a normal urine Ca2+/creatinine ratio. Kidney International 1998 54, 1396-1410DOI: (10.1046/j.1523-1755.1998.00124.x) Copyright © 1998 International Society of Nephrology Terms and Conditions

Figure 3 Predicted amino acid sequence of paternal (F) and maternal (M) NCCT polypeptides in the presented patient with GS. Messenger RNA was isolated from peripheral blood mononuclear cells obtained from normals and from the patient under discussion with GS. Following reverse transcription with AMV reverse transcriptase, NCCT cDNA was amplified by PCR and sequenced. Genomic DNA from the patient and his parents also was sequenced to determine the inheritance of each allele. Two different mutations were detected in the patient’s NCCT cDNA (compound heterozygote). The cDNA from the patient’s paternal allele had an additional 119bp insertion between exon 3 and 4, generating a predicted premature stop codon after amino acid 187. In cDNA from the maternal allele, exon 24 was deleted, resulting in a predicted premature stop codon after amino acid 920. Kidney International 1998 54, 1396-1410DOI: (10.1046/j.1523-1755.1998.00124.x) Copyright © 1998 International Society of Nephrology Terms and Conditions

Figure 4 The severity of hypokalemia in type-1 (NKCC2, □) versus type-2 (ROMK, ○) and type-3 (ClC-Kb, ▵) Bartter’s syndrome mutations. Mean serum potassium in type-1 BS was 2.2 ± 0.24mEq/liter, 3.3 ± 0.08mEq/liter in type-2 BS, and 2.4 ± 0.12mEq/liter in type-3 BS. The data in patients with ROMK mutations were obtained from Derst et al117. The data in patients with NKCC2 mutations came from Simon et al86. The data in patients with ClC-Kb mutations were from Ref. 128. * P < 0.001. Kidney International 1998 54, 1396-1410DOI: (10.1046/j.1523-1755.1998.00124.x) Copyright © 1998 International Society of Nephrology Terms and Conditions

Figure 5 Localization of transport abnormalities in Gitelman’s and Bartter’s syndromes. Kidney International 1998 54, 1396-1410DOI: (10.1046/j.1523-1755.1998.00124.x) Copyright © 1998 International Society of Nephrology Terms and Conditions

Kidney International 1998 54, 1396-1410DOI: (10. 1046/j. 1523-1755 Kidney International 1998 54, 1396-1410DOI: (10.1046/j.1523-1755.1998.00124.x) Copyright © 1998 International Society of Nephrology Terms and Conditions

Kidney International 1998 54, 1396-1410DOI: (10. 1046/j. 1523-1755 Kidney International 1998 54, 1396-1410DOI: (10.1046/j.1523-1755.1998.00124.x) Copyright © 1998 International Society of Nephrology Terms and Conditions

Kidney International 1998 54, 1396-1410DOI: (10. 1046/j. 1523-1755 Kidney International 1998 54, 1396-1410DOI: (10.1046/j.1523-1755.1998.00124.x) Copyright © 1998 International Society of Nephrology Terms and Conditions