Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1.
Autosomal recessive pseudohypoaldosteronism type I is a rare life-threatening disease characterized by severe neonatal salt wasting, hyperkalaemia, metabolic acidosis, and unresponsiveness to mineralocorticoid hormones. Investigation of affected offspring of consanguineous union reveals mutations in either the alpha or beta subunits of the amiloride-sensitive epithelial sodium channel in five kindreds. These mutations are homozygous in affected subjects, co-segregate with the disease, and introduce frameshift, premature termination or missense mutations that result in loss of channel activity. These findings demonstrate the molecular basis and explain the pathophysiology of this disease.
Chang
S S
SS
Howard Hughes Medical Institute, Department of Genetics, Boyer Center for Molecular Medicine.
Grunder
S
S
Hanukoglu
A
A
Rösler
A
A
Mathew
P M
PM
Hanukoglu
I
I
Schild
L
L
Lu
Y
Y
Shimkets
R A
RA
Nelson-Williams
C
C
Rossier
B C
BC
Lifton
R P
RP
D000818:Animals; D001483:Base Sequence; D004247:DNA; D053503:Epithelial Sodium Channels; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011546:Pseudohypoaldosteronism / Q000145:classification / Q000235:genetics*; D051381:Rats; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism
D053503:Epithelial Sodium Channels; D015222:Sodium Channels; D004247:DNA