Liddle's syndrome caused by a novel mutation in the proline-rich PY motif of the epithelial sodium channel beta-subunit.
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Furuhashi M, Kitamura K, Adachi M, Miyoshi T, Wakida N, Ura N, Shikano Y, Shinshi Y, Sakamoto K, Hayashi M, Satoh N, Nishitani T, Tomita K, Shimamoto K
Liddle's syndrome caused by a novel mutation in the proline-rich PY motif of the epithelial sodium channel beta-subunit.
J Clin Endocrinol Metab. 2005 Jan;90(1):340-4. Epub 2004 Oct 13.
- PubMed ID
- 15483078 [ View in PubMed]
- Abstract
Liddle's syndrome is an autosomal dominant form of salt-sensitive hypertension and has been shown to be caused by missense or frameshift mutations in the amiloride-sensitive epithelial sodium channel (ENaC), which is composed of three subunits: alpha, beta, and gamma. All disease mutations either remove or alter amino acids of the target proline-rich PPPxY sequence (PY motif) of beta- or gamma-ENaC and result in increased channel activity. In this report, we present a family with Liddle's syndrome whose abnormality is caused by a novel missense mutation, P616R, in the PY motif of the betaENaC. Functional studies using the P616R mutant expressed in Xenopus oocytes showed an approximately 6-fold increase in the amiloride-sensitive sodium channel activity compared with that of the wild type. These findings provide additional clinical evidence that a conserved PY motif is critically important for the regulation of ENaC activity.