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Endocrine

, Volume 29, Issue 3, pp 385–390 | Cite as

Mutation analysis of SCNN1B in a family with Liddle's syndrome

  • Weiqing Wang
  • Weiwei Zhou
  • Lei Jiang
  • Bin Cui
  • Lei Ye
  • Tingwei Su
  • Jiguang Wang
  • Xiaoying Li
  • Guang Ning
Original Articles

Abstract

Liddle's syndrome has been known as a disorder associated with abnormal sodium reabsorption in the distal tubule and transmitted as a rare autosomal dominant trait. It is caused by mutations in the SCNN1B or SCNN1C gene, which truncate the cytoplasmic carboxyl terminus of the β and γ subunit of the epithelial sodium channel (ENaC). Genetic analysis of ENaC in a Chinese family with Liddle's syndrome revealed P616H of SCNN1B coaggregated with the phenotype, while this variant was not detected in 100 unrelated subjects. No mutation at γ ENaC could be detected in all members of the family. P616H is located in the conserved proline-rich PY motif of the βENaC. The PY motif can interact with the WW domain in Nedd4 and affect the activity of ENaC. Structural bioinformatics analysis confirmed that the functional interaction between Nedd4 and ENaC reduces in Liddle-ENaC (P616H) when compared with wild-type ENaC. In summary, P616H may be an underlying mechanism for the signs and symptoms of this family.

Key Words

Liddle's syndrome epithelial sodium channel hereditary disease hypertension 

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Copyright information

© Humana Press Inc. 2006

Authors and Affiliations

  • Weiqing Wang
    • 1
    • 2
  • Weiwei Zhou
    • 1
  • Lei Jiang
    • 1
  • Bin Cui
    • 1
    • 3
  • Lei Ye
    • 1
  • Tingwei Su
    • 1
  • Jiguang Wang
    • 2
    • 4
  • Xiaoying Li
    • 2
    • 3
  • Guang Ning
    • 1
    • 2
    • 3
  1. 1.Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, Ruijin HospitalShanghai Jiaotong University Medical SchoolShanghaiP.R. China 200025
  2. 2.the Endocrine and Metabolic DivisionE-Institutes of Shanghai UniversitiesShanghaiP.R. China
  3. 3.Health Science Center, Shanghai Institute for Biological SciencesChinese Academy of Sciences and Shanghai Jiaotong University Medical SchoolShanghaiPR China
  4. 4.Center for Epidemiological Studies and Clinical Trials, Ruijin HospitalShanghai Jiaotong University Medical SchoolShanghaiP.R. China

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