A novel epithelial sodium channel gamma-subunit de novo frameshift mutation leads to Liddle syndrome.

Abstract

OBJECTIVE:

Liddle syndrome is a rare autosomal-dominant monogenic form of hypertension caused by mutations in the C-termini of the epithelial sodium channel beta- or gamma-subunit encoded by SCNN1B and SCNN1G, respectively, and often presenting with a familial history of hypertension. The purpose of this study was to determine whether mutations of SCNN1B or SCNN1G were present in a patient clinically suspected to have Liddle syndrome with no familial history of hypertension.

DESIGN AND PATIENTS:

We screened the C-terminus of SCNN1B and SCNN1G in the patient, and also screened for the mutation in his parents, 50 hypertensive patients and 50 controls.

RESULTS:

In this patient, no mutations were found in the C-terminus of SCNN1B. However, we found a frameshift mutation caused by an 'AGCTC' deletion at the 583 codon in SCNN1G. The frameshift resulted in a new termination site at the 585 codon of the gamma-subunit and the deletion of its PY motif. Neither his parents nor 50 randomly selected patients with hypertension nor 50 controls have the mutation, indicating that this is a de novo mutation and not a common genetic polymorphism.

CONCLUSION:

The de novo mutation is the first reported frameshift of the gamma-subunit causing Liddle syndrome. These data imply that a familial history of hypertension is not an essential criterion for the diagnosis of Liddle syndrome.

• Authors: Yibo Wang, Yi Zheng, Jinxing Chen, Haiying Wu, Deyu Zheng, Rutai Hui
• Journal: Clinical endocrinology (Clin Endocrinol (Oxf)) Vol. 67 Issue 5 Pg. 801-4 (Nov 2007) ISSN: 0300-0664 [Print] England
• PMID: 17634077 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Epithelial Sodium Channels
• SCNN1B protein, human

Topics

• Adolescent
• Amino Acid Sequence
• Base Sequence
• Case-Control Studies
• Epithelial Sodium Channels (genetics)
• Frameshift Mutation
• Genes, Dominant
• Heterozygote
• Humans
• Hypertension (genetics)
• Male
• Molecular Sequence Data