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A novel epithelial sodium channel γ‐subunit de novo frameshift mutation leads to Liddle syndrome
Author(s) -
Wang Yibo,
Zheng Yi,
Chen Jinxing,
Wu Haiying,
Zheng Deyu,
Hui Rutai
Publication year - 2007
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2007.02967.x
Subject(s) - frameshift mutation , genetics , mutation , stop codon , medicine , epithelial sodium channel , endocrinology , biology , gene , sodium , chemistry , organic chemistry
Summary Objective Liddle syndrome is a rare autosomal‐dominant monogenic form of hypertension caused by mutations in the C‐termini of the epithelial sodium channel β‐ or γ‐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 γ‐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 γ‐subunit causing Liddle syndrome. These data imply that a familial history of hypertension is not an essential criterion for the diagnosis of Liddle syndrome.