Simon DB, Karet FE, Hamdan JH, DiPietro A, Lifton RP
Bartter's syndrome is caused by mtations in the Na-K-2Cl
cotransporter
50th Annual Fall Conference AHA Council for High Blood Pressure
Research
Hypertens
(Sep) 28:513 1996
Bartter's syndrome is a rare cause of hypokalemic metabolic alkalosis
with hypomagnesemia and hypercalciuria in which blood pressure is
normal or low. The syndrome has been supposed to be caused by a
defect in the Na-K-2Cl (NKCC2) cotransporter in the thick ascending
limb of Henle because of concomitant renal salt wasting, impaired
maximal urinary concentrating capacity, attenuation of salt wasting
after NSAIDS which block prostaglandin E2, a known inhibitor NaCl in
this segment.
In this study, Simon et al provide strong evidence in favor of
mutations in the NKCC2 cotransporter as the cause of he Bartter's
syndrome phenotype. They collected samples from consanguineous
kindreds segregating for Bartter's syndrome and cloned the human
homolog of NKCC2, then mapped the gene and screened for mutations in
affected subjects. Homozygous mutations were found in all affected
including two frameshift and one splice site mutation all of which
resulted in truncated proteins. Also a substitute of phenylalanine
for valine in the transmembrane component of the protein was found in
one patient.
Comment: This exciting work provides strong support for
mutations in the NKCC2 as causal in Bartter's syndrome. It would be
interesting to know whether functional aspects of the separate
mutations are the same or similar. No data on electrolyte metabolism
or renal function were provided in the study subjects; therefore the
functional expression could not be ascertained. Still, this is an
exciting piece of work and is of great interest in the genetic studies
of hypertension and related syndromes. As the authors point out, this
type of analysis now allows them to assess the contribution of the
heterozygous state to reduced blood pressure and other phenotypes.
(Robert D. Toto, M.D., University of Texas Southwestern Medical
Center)
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50th Annual Fall Conference AHA Council for High Blood Pressure
Research
Acidosis/alkalosis :
Hypokalemia