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Monogenic forms of human hypertension

  • Hakan R. Toka
    Affiliations
    Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, CT; and the Franz Volhard Clinic and Max Delbrück Center for Molecular Medicine, Helios Klinikum, Medical Faculty of the Charité, Humboldt University of Berlin, Germany
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  • Friedrich C. Luft
    Affiliations
    Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, CT; and the Franz Volhard Clinic and Max Delbrück Center for Molecular Medicine, Helios Klinikum, Medical Faculty of the Charité, Humboldt University of Berlin, Germany
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      Abstract

      Monogenic or Mendelian forms of hypertension have ushered in a revolution in our knowledge. If we add information on syndromes involving low blood pressure, this knowledge base is doubled. Glucocorticoid-remediable aldosteronism, apparent mineralocorticoid excess, and mutations in the mineralocorticoid receptor gene have given us brilliant insights into mineralocorticoid-induced hypertension. The latter discovery has elucidated how mutations may modify the receptor sufficiently to allow erstwhile antagonists to have an agonistic action. The epithelial sodium channel (ENaC) has been elucidated. Gain-of-function mutations in the β and γ subunits of ENaC cause Liddle's syndrome. Loss-of-function mutations in all 3 subunits of ENaC cause hypotension (pseudohypoaldosteronism type I). Thus, all 3 subunits can be mutated, causing either hyper- or hypotension. Three loci have been described for Gordon's syndrome, pseudohypoaldosteronism type II; 2 members of the WNK (with no ly sine K) serine-threonine kinase family have recently been found to be responsible. Autosomal-dominant hypertension with brachydactyly features normal sodium and renin-angiotensin-aldosterone responses. The gene has been mapped to chromosome 12p. The condition is interesting because it may represent a novel neural form of hypertension. The elucidation of Mendelian blood pressure–regulatory disorders has been a resounding success. Copyright 2002, Elsevier Science (USA). All rights reserved.
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