A Unique Genotype of Pseudohypoaldosteronism Type 1b in a Highly Consanguineous Population.

CONTEXT

Pseudohypoaldosteronism (PHA) is a condition in which serum aldosterone level is normal or elevated but its action is deficient.

OBJECTIVE

This study describes the molecular genetics of PHA 1b in the highly consanguineous population of 2 Arabian Gulf countries, Saudi Arabia and Oman.

METHODS

This study enrolled 22 patients from 13 unrelated families (2 families with 5 patients from Oman and 11 families with 17 patients from Saudi Arabia). All of these patients had presented within the first 10 days of life with nausea and vomiting, hyponatremia, hyperkalemia, and hypotension. We isolated DNA from peripheral blood and PCR-sequenced all exons and exon-intron boundaries of and, if negative, and using the Dideoxy Chain termination method.

RESULTS

We found a total of 8 mutations in 13 families as follows: 6 mutations in , 1 in , and 1 in . All of these mutations were novel except one. mutations were: c.1496A>G, p.Q499R (novel) in 1 patient; c.1453C>T, p.Q485X (novel) in 1 patient; c.1322_1322delA, p.N441Tfs41 (novel) in 2 patients of 1 family; c.876 + 2 delGAGT (novel) in 3 patients of 1 family; c.203_204 delTC, p.I68Tfs76 (a known mutation) in 8 patients of 5 families; and whole gene deletion (novel) in 2 patients of 2 families. In addition, a nonsense mutation c.1694C>A, p.S565X (novel) was found in 3 siblings from 1 Omani family, and an deletion mutation c.527_528 delCA, p.T176Rfs*9 (novel) in 2 siblings from another Omani family.

CONCLUSION

We characterized a unique genotype of PHA 1b with several novel gene structure-disrupting mutations in , , and in a highly consanguineous population.