Genetic analysis of the epithelial sodium channel in Liddle's syndrome

Liddle's syndrome is an autosomal inheritable disorder that causes hypertension due to excess function of sodium channel.

To analyze the DNA sequence of the amiloride-sensitive epithelial sodium channel (ENaC) in three patients who had low-renin hypertension with hypokalemia. The patients included a 24-year-old woman and her 20-year-old brother whose mother was hypertensive. The third patient was a 15-year-old girl with no family history of hypertension.

The DNA sequence of the ENaC was analyzed as follows. Venous blood samples were collected from the patients and total genomic DNA was prepared by standard methods. Specific primers were used for direct polymerase chain reaction; one set of primers for amplifying the C terminus (codon 523-638) of the , subunit of ENaC, and two sets of primers for amplifying the C terminus (codons 525-587 and 568-650) of the y subunit of ENaC. Polymerase chain reaction products were purified and subjected to direct DNA sequence analysis.

Direct sequence analysis demonstrated the presence of a single-base substitution in one segment of the 0 subunit of ENaC, a C-T transition that changed the encoded Pro (CCC) at codon 616 to Ser (TCC) in the siblings (cases 1 and 2). In case 3, we found a missense mutation of Pro (CCC) to Leu (CTC) at codon 616. Case 3 is considered to be sporadic, since DNA sequencing of the PY motif of her parents gave normal results.

The DNA sequences of the ENaC in three patients with Liddle's syndrome were analyzed. In one family case, we found a new missense mutation of Pro (CCC) to Ser (TCC) at codon 616 in the 0 subunit of ENaC. A genetic analysis of the amiloride-sensitive epithelial sodium channel is recommended in assessing patients with low-renin, salt-sensitive hypertension whose blood pressure is not responsive to spironolactone treatment.