Human Hypertension Caused by Mutations in WNK Kinases
2001; American Association for the Advancement of Science; Volume: 293; Issue: 5532 Linguagem: Inglês
10.1126/science.1062844
ISSN1095-9203
AutoresFrederick H. Wilson, Sandra Disse-Nicodème, Keith A. Choate, Kazuhiko Ishikawa, Carol Nelson‐Williams, Isabelle Desitter, Murat Günel, David V. Milford, Graham Lipkin, Jean‐Michel Achard, Morgan Feely, Bertrand Dussol, Yvon Berland, Robert J. Unwin, Haim Mayan, David B. Simon, Zvi Farfel, Xavier Jeunemaı̂tre, Richard P. Lifton,
Tópico(s)Diabetes Treatment and Management
ResumoHypertension is a major public health problem of largely unknown cause. Here, we identify two genes causing pseudohypoaldosteronism type II, a Mendelian trait featuring hypertension, increased renal salt reabsorption, and impaired K + and H + excretion. Both genes encode members of the WNK family of serine-threonine kinases. Disease-causing mutations in WNK1 are large intronic deletions that increase WNK1 expression. The mutations in WNK4 are missense, which cluster in a short, highly conserved segment of the encoded protein. Both proteins localize to the distal nephron, a kidney segment involved in salt, K + , and pH homeostasis. WNK1 is cytoplasmic, whereas WNK4 localizes to tight junctions. The WNK kinases and their associated signaling pathway(s) may offer new targets for the development of antihypertensive drugs.
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