1998 Fiscal Year Final Research Report Summary
The analysis of the gene of a family with Liddle's syndrome
| Project/Area Number |
09671170
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Kumamoto University |
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Principal Investigator |
TOKUNAGA Hiroshi University Internal medicine, Assistant Professor, 医学部・附属病院, 助手 (00305012)
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| Co-Investigator(Kenkyū-buntansha) |
TOMITA Kimio University Internal medicine, Professor, 医学部, 教授 (40114772)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Liddle's syndrome / epithelial sodium channel / nitric oxide synthase |
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| Research Abstract |
Liddle's syndrome is an autosomal dominant form of salt sensitive hypertension caused by mutations in the beta or gamma subunit of the epithelial sodium channel. Systematic mutagenesis studies revealed that a conserved PPPXY sequence (PY motif) of the C-terminus of the alpha, beta, or gamma subunits might be involved in the regulation of the channel activity. However, only two missense mutations in the PY motif of the beta subunit have been reported to cause Liddle's syndrome. We sequenced the C-termini of the beta and gamma subunits of the epithelial sodium channel in a Japanese family clinically diagnosed as having Liddle's syndrome and found a new missense mutation in the PY motif of the beta subunit, P615S.Expression studies with P615S mutant in Xenopus oocytes resulted in an about 3-fold increase in the amiloride-sensitive sodium current compared to the wild type (p=0.001). These findings provide further clinical evidence for the hypothesis that a conserved PY motif may be critically important for the regulation of the epithelial sodium channel.
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