Liddle's syndrome caused by a novel mutation in the proline-rich PY motif of the epithelial sodium channel beta-subunit
| Autor: | Naotoshi Satoh, Ken Ichi Sakamoto, Kimio Tomita, Yasukuni Shikano, Masataka Adachi, Kazuaki Shimamoto, Yasuyuki Shinshi, Taku Miyoshi, Takahiro Nishitani, Kenichiro Kitamura, Masato Furuhashi, Naoki Wakida, Nobuyuki Ura, Manabu Hayashi |
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| Rok vydání: | 2004 |
| Předmět: |
Epithelial sodium channel
Adult medicine.medical_specialty Proline Endocrinology Diabetes and Metabolism Xenopus Clinical Biochemistry Mutant Amino Acid Motifs Mutation Missense Biology medicine.disease_cause Biochemistry Sodium Channels Frameshift mutation Endocrinology Internal medicine medicine Missense mutation Animals Humans Liddle's syndrome Child Epithelial Sodium Channels Aged Sodium channel activity Mutation Biochemistry (medical) Wild type Syndrome medicine.disease Protein Subunits Hypertension Female |
| Zdroj: | The Journal of clinical endocrinology and metabolism. 90(1) |
| ISSN: | 0021-972X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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