Analysis of claudin genes in pediatric patients with Bartter's syndrome.
Bartter's syndrome is a constellation of symptoms characterized by hyper-reninemic hypokalemia, metabolic alkalosis, elevated renin and aldosterone, low or normal blood pressure, and hyperplasia of the juxtaglomerular apparatus. So far, five gene mutations in proteins regulating the sodium chloride transport in the thick ascending limb of Henle's loop have been described. However, the molecular mechanisms underlying the presentation of hypomagnesemia in some of these patients remains unclear. Claudins are a family of transmembranous proteins within the tight junctions that have been shown to be important for the paracellular movement of ions. Mutations in claudin-16 have been identified in patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis. To test the hypothesis that mutations in claudin genes may be involved in the altered magnesium and calcium transport in Bartter's syndrome, we began to examine the genes of claudins known to be present in renal tubules in four pediatric patients with Bartter's syndrome. All four patients were African Americans with hypomagnesemia and hypercalciuria. In this study, we did not find any mutation in the coding regions of claudin-2, -3, -4, -7, -8, -10, -11, or -16 genes in these patients. However, all patients had a single nucleotide substitution of C for T at the position of 451 of claudin-8 gene sequence that changes amino acid residue from serine to proline at the position of 151 in the second extracellular domain of claudin-8 protein. The significance of this known single nucleotide polymorphism remains to be determined.
Chen
Yan-Hua
YH
Department of Anatomy and Cell Biology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA.
Lin
Jen-Jar
JJ
Jeansonne
Beverly G
BG
Tatum
Rodney
R
Lu
Qun
Q
D000293:Adolescent; D001477:Bartter Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D002648:Child; D005260:Female; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction
D008565:Membrane Proteins; D008274:Magnesium; D002118:Calcium