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

Objective To identify the gene mutation in β and γ 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 diagn...

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Bibliographic Details
Published in:The Journal of pediatrics 2013, Vol.162 (1), p.166-170
Main Authors: Gao, Linggen, MD, Wang, Linping, MD, Liu, Yaxin, MD, Zhou, Xianliang, MD, Hui, Rutai, MD, Hu, Aihua, MD, PhD
Format: Article
Language:English
Subjects:
Adolescent
adolescents
Adult
Aged
boys
Epithelial Sodium Channels - genetics
Female
genes
heterozygosity
Humans
hypertension
hypokalemia
Liddle Syndrome - genetics
Male
Middle Aged
missense mutation
Mutation, Missense
patients
Pediatrics
Pedigree
risk
sequence analysis
sodium channels
therapeutics
Young Adult
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Summary:Objective To identify the gene mutation in β and γ 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 β 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 β or γ 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.
ISSN:0022-3476
1097-6833
DOI:10.1016/j.jpeds.2012.06.017