title: Monogenic forms of human hypertension.
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 beta and gamma 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.
authors.affiliation: Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Hakan R
authors.initials: HR
authors.lastname: Toka
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
mesh_terms: D006801:Humans; D006929:Hyperaldosteronism / Q000235:genetics*; D006973:Hypertension / Q000235:genetics*; D011546:Pseudohypoaldosteronism / Q000235:genetics*; D018161:Receptors, Mineralocorticoid / Q000235:genetics* / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D013577:Syndrome
chemical_list: D018161:Receptors, Mineralocorticoid; D013254:Steroid 17-alpha-Hydroxylase