A Family with Liddle Syndrome Caused by a Novel Missense Mutation in the PY Motif of the Beta-Subunit of the Epithelial Sodium Channel

作者：Gao, Linggen; Wang, Linping; Liu, Yaxin; Zhou, Xianliang^*; Hui, Rutai; Hu, Aihua

来源：Journal of Pediatrics, 2013, 162(1): 166-170.

DOI：10.1016/j.jpeds.2012.06.017

• GAMMA-SUBUNIT
• FRAMESHIFT MUTATION
• GENETIC-ANALYSIS
• NA+ CHANNEL
• HYPERTENSION
• IDENTIFICATION
• DIAGNOSIS
• DISEASE

Objective To identify the gene mutation in beta and gamma subunits of the epithelial sodium channel (ENaC) in an adolescent and family members with Liddle syndrome, an autosomal dominant form of secondary hypertension.
Study design We screened an adolescent with severe hypertension who was clinically diagnosed with Liddle syndrome for mutations in the C-terminus of the SCNN1B and SCNN1G genes. We also screened for these mutations in his family members, in 100 hypertensive patients, and in 100 controls.
Results The index case, a 14-year-old boy, was diagnosed with Liddle syndrome by the identification of a novel missense mutation, P614L, in the PY motif of the beta subunit of the ENaC. Testing of relatives considered at risk revealed 6 subjects heterozygous for the mutation. All genetically affected subjects had a history of severe hypertension as well as hypokalemia. No other variants in the beta or gamma subunits of the ENaC were detected.
Conclusion Based on direct DNA sequencing, we have detected a novel mutation that causes Liddle syndrome. This confirms the diagnosis and helps guide effective therapy for this adolescent and his affected relatives. These findings provide further evidence that the conserved PY motif is critical to regulation of ENaC activity. (J Pediatr 2013;162:166-70).

• 出版日期2013-1
• 单位中国人民解放军总医院; 中国医学科学院北京协和医院; 中国医学科学院阜外医院; 北京协和医学院