A novel frameshift mutation of epithelial sodium channel β-subunit leads to Liddle syndrome in an isolated case.
OBJECTIVE
Liddle syndrome, an autosomal dominant form of monogenic hypertension, is attributed to mutations in the genes encoding β and γ subunits (SCNN1B and SCNN1G) of the epithelial sodium channel (ENaC). The aim of this study was to search for pathogenic mutations of SCNN1B and SCNN1G in an adolescent under the impression of Liddle syndrome and no family history of hypertension.


METHODS
We screened the C-terminus of SCNN1B and SCNN1G in an adolescent with poorly controlled hypertension who was clinically diagnosed as having Liddle syndrome. We also screened for the mutation in his parents, 100 hypertensive patients and 100 controls.


RESULTS
Genetic analysis of SCNN1B revealed a frameshift mutation induced by insertion of an additional cytosine into a string of six located between codons 617 and 618, which is predicted to introduce a new termination codon at position 621 and produce a protein truncated by 20 amino acids. This frameshift mutation was not detected in the patient's parents, the 100 hypertensive patients or the 100 controls, indicating that this is a de novo mutation and not a common genetic polymorphism. There was no mutation of SCNN1G in any of the individuals examined.


CONCLUSIONS
Based on direct DNA sequencing, we identified a novel frameshift mutation in the βENaC gene in an isolated case of Liddle syndrome. Confirmation of the diagnosis and effective tailored treatment in the patient were achieved, implying that genetic testing is a useful tool to diagnose Liddle syndrome.
Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Kun-Qi
KQ
Yang
Chao-Xia
CX
Lu
Yan
Y
Xiao
Ya-Xin
YX
Liu
Xiong-Jing
XJ
Jiang
Xue
X
Zhang
Xian-Liang
XL
Zhou
D000293:Adolescent; D053503:Epithelial Sodium Channels / Q000235:genetics*; D016368:Frameshift Mutation; D006579:Heterozygote; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics / Q000378:metabolism; D007008:Hypokalemia / Q000097:blood; D056929:Liddle Syndrome / Q000235:genetics*; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA
D053503:Epithelial Sodium Channels; C507048:SCNN1B protein, human; C507052:SCNN1G protein, human