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.


METHODS
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.


CONCLUSIONS
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.
Department of Cardiology, FuWai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Linggen
L
Gao
Linping
L
Wang
Yaxin
Y
Liu
Xianliang
X
Zhou
Rutai
R
Hui
Aihua
A
Hu
D000293:Adolescent; D000328:Adult; D000368:Aged; D053503:Epithelial Sodium Channels / Q000235:genetics*; D005260:Female; D006801:Humans; D056929:Liddle Syndrome / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D055815:Young Adult
D053503:Epithelial Sodium Channels; C507048:SCNN1B protein, human