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Masato Furuhashi, Kenichiro Kitamura, Masataka Adachi, Taku Miyoshi, Naoki Wakida, Nobuyuki Ura, Yasukuni Shikano, Yasuyuki Shinshi, Ken-ichi Sakamoto, Manabu Hayashi, Naotoshi Satoh, Takahiro Nishitani, Kimio Tomita, Kazuaki Shimamoto, Liddle’s Syndrome Caused by a Novel Mutation in the Proline-Rich PY Motif of the Epithelial Sodium Channel β-Subunit, The Journal of Clinical Endocrinology & Metabolism, Volume 90, Issue 1, 1 January 2005, Pages 340–344, https://doi.org/10.1210/jc.2004-1027
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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: α, β, and γ. All disease mutations either remove or alter amino acids of the target proline-rich PPPxY sequence (PY motif) of β- or γ-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 βENaC. 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.
