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

作者：Wang, Yibo^*; Zheng, Yi; Chen, Jinxing; Wu, Haiying; Zheng, Deyu; Hui, Rutai

来源：Clinical Endocrinology, 2007, 67(5): 801-804.

DOI：10.1111/j.1365-2265.2007.02967.x

• BETA-SUBUNIT
• MISSENSE MUTATION
• GENETIC-ANALYSIS
• NA+ CHANNEL
• FAMILY
• HYPERTENSION
• IDENTIFICATION
• DISORDER
• DISEASE

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.

• 出版日期2007-11
• 单位中国医学科学院北京协和医院; 中国医学科学院阜外医院