A frameshift mutation of beta subunit of epithelial sodium channel in a case of isolated Liddle syndrome.
BACKGROUND
Liddle syndrome is an autosomal dominant form of salt-sensitive hypertension caused by mutations in the epithelial sodium channel expressed in the distal nephron playing an essential role in Na absorption. All reported mutations in Liddle syndrome are either missense mutations or frameshift mutations destroying the PY motif closer to the C-terminus of the beta or gamma subunits causing the situation that the epithelial sodium channels are not degraded and sodium is pooled and thus hypertension and hypokalemia are caused.


METHODS
We sequenced the C-terminus of the beta or gamma subunits of the epithelial sodium channel in a Japanese family of a patient clinically diagnosed as having Liddle syndrome.


RESULTS
As a result, we found in the proband, a frameshift mutation of the beta subunit caused by a single cytosine insertion at the codon 595, introducing a new stop codon at 605 and deleting the last 34 amino acids from the normally encoded protein.


CONCLUSIONS
This mutation is carried by neither parent (with paternity proven) and hence confirms this has occurred as a event within this family.
Nakano
Yukiko
Y
Department of Medicine and Molecular Science, Hiroshima University Graduate School of Medicine, Japan. nakanoy@hiroshima-u.ac.jp
Ishida
Takafumi
T
Ozono
Ryoji
R
Matsuura
Hideo
H
Yamamoto
Yuji
Y
Kambe
Masayuki
M
Chayama
Kazuaki
K
Oshima
Tetsuya
T
D000293:Adolescent; D000471:Alkalosis / Q000235:genetics*; D000595:Amino Acid Sequence / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D053503:Epithelial Sodium Channels; D005260:Female; D016368:Frameshift Mutation; D005799:Genes, Dominant; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007008:Hypokalemia / Q000235:genetics*; D008969:Molecular Sequence Data; D015222:Sodium Channels / Q000235:genetics*; D013577:Syndrome
D053503:Epithelial Sodium Channels; C507048:SCNN1B protein, human; D015222:Sodium Channels