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      K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension.

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          Abstract

          Endocrine tumors such as aldosterone-producing adrenal adenomas (APAs), a cause of severe hypertension, feature constitutive hormone production and unrestrained cell proliferation; the mechanisms linking these events are unknown. We identify two recurrent somatic mutations in and near the selectivity filter of the potassium (K(+)) channel KCNJ5 that are present in 8 of 22 human APAs studied. Both produce increased sodium (Na(+)) conductance and cell depolarization, which in adrenal glomerulosa cells produces calcium (Ca(2+)) entry, the signal for aldosterone production and cell proliferation. Similarly, we identify an inherited KCNJ5 mutation that produces increased Na(+) conductance in a Mendelian form of severe aldosteronism and massive bilateral adrenal hyperplasia. These findings explain pathogenesis in a subset of patients with severe hypertension and implicate loss of K(+) channel selectivity in constitutive cell proliferation and hormone production.

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          Author and article information

          Journal
          Science
          Science (New York, N.Y.)
          American Association for the Advancement of Science (AAAS)
          1095-9203
          0036-8075
          Feb 11 2011
          : 331
          : 6018
          Affiliations
          [1 ] Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
          Article
          331/6018/768 HHMIMS379267
          10.1126/science.1198785
          3371087
          21311022
          dbbee7b2-b331-4af5-9821-9484aea0b3f9

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