Diagnosis of Liddle syndrome by genetic analysis of beta and gamma subunits of epithelial sodium channel--a report of five affected family members.
OBJECTIVE
To screen the gene mutation in beta and gamma subunits of the epithelial sodium channel (ENaC) of a Chinese family, some of whose members are clinically diagnosed as suffering from Liddle syndrome.


METHODS
Twelve family members were recruited to the study. Among them, two brothers had been clinically diagnosed as suffering from Liddle syndrome. Peripheral blood samples were collected from all members of the family and total genomic DNA was prepared for genetic analysis. Polymerase chain reaction (PCR) was used for amplifying the last exon of beta (codon 513-673) and gamma (codon 503-632) subunits of the ENaC gene. PCR products were purified and subjected to a direct DNA sequence analysis.


RESULTS
Genetic analysis of the beta ENaC gene revealed a missense mutation of CCC to CTC at codon 616 in four middle-aged men of the second generation and one young woman of the third generation. There was no mutation of the gamma ENaC gene in any of the individuals examined.


CONCLUSIONS
Through direct DNA sequencing analysis, we diagnosed the disease present in five members of a Chinese family as Liddle syndrome, and excluded it in some other young offspring suffering from the monogenic disease. Our results provide further evidence that Pro616 is a critical amino acid that has a key role in the inhibition of sodium channel activity.
Gao
P J
PJ
Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Second Medical University, People's Republic of China.
Zhang
K X
KX
Zhu
D L
DL
He
X
X
Han
Z Y
ZY
Zhan
Y M
YM
Yang
L W
LW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000378:metabolism*; D001483:Base Sequence / Q000235:genetics; D002648:Child; D004247:DNA / Q000235:genetics; D053503:Epithelial Sodium Channels; D005260:Female; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007008:Hypokalemia / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D020033:Protein Isoforms / Q000235:genetics; D012083:Renin / Q000097:blood*; D015222:Sodium Channels / Q000235:genetics*; D013577:Syndrome
D053503:Epithelial Sodium Channels; D020033:Protein Isoforms; C507048:SCNN1B protein, human; D015222:Sodium Channels; D000450:Aldosterone; D004247:DNA; D012083:Renin