Pendred syndrome: Phenotypic variability in two families carrying the samePDS missense mutation

Pendred syndrome comprises congenital sensorineural hearing loss, thyroid g oiter, and positive perchlorate discharge test, Recently, this autosomal re cessive disorder was shown to be caused by mutations in the PDS gene, which encodes an anion transporter called pendrin. Molecular analysis of the PDS gene was performed in two consanguineous large families from Southern Tuni sia comprising a total of 23 individuals affected with profound congenital deafness; the same missense mutation, L445W, was identified in all affected individuals. A widened vestibular aqueduct was found in all patients who u nderwent computed tomography (CT) scan exploration of the inner ear. In con trast, goiter was present in only 11 affected individuals, who interestingl y had a normal result of the perchlorate discharge test whenever performed. The present results question the sensitivity of the perchlorate test for t he diagnosis of Pendred syndrome and support the use of a molecular analysi s of the PDS gene in the assessment of individuals with severe to profound congenital hearing loss associated with inner ear morphological anomaly eve n in the absence of a thyroid goiter. Am. J. Med. Genet. 90:38-44, 2000. (C ) 2000 Wiley-Liss, Inc.