THE DIAGNOSIS OF LIDDLE-SYNDROME BY IDENTIFICATION OF A MUTATION IN THE BETA-SUBUNIT OF THE EPITHELIAL SODIUM-CHANNEL

Hypertension is a common multifactorial disorder associated with consi derable morbidity and mortality. The kidney plays a major role in the long term regulation of blood pressure. Liddle syndrome (pseudo-hypera ldosteronism) is one of a number of monogenic disorders of salt and wa ter transport. In a kindred with at least four affected members suffer ing from Liddle syndrome, we confirmed by direct DNA sequencing the id entity of a novel heterozygous mutation in h beta ENaC, the gene encod ing the beta subunit of the amiloride sensitive epithelial sodium chan nel which is expressed in the distal nephron. Single stranded conforma tional polymorphism analysis showed cosegregation of the mutant allele within the kindred with the Liddle phenotype, An insertion of an addi tional cytosine into a string of six located between codons 593 and 59 5 results in a sequence frameshift and is predicted to produce a prote in truncated by 34 amino acids. The availability of a molecular diagno stic tool has implications for the management of hypertension and gene tic counselling in families with Liddle syndrome.