Journal article Open Access
Everett, Lorraine A.; Glaser, Benjamin; Beck, John C.; Idol, Jacquelyn R.; Buchs, Andreas; Heyman, Ma'ayan; Adawi, Faiad; Hazani, Elizur; Nassir, Elias; Baxevanis, Andreas D.; Sheffield, Val C.; Green, Eric D.
Pendred syndrome is a recessively inherited disorder with the hallmark features of congenital deafness and thyroid goitre. By some estimates, the disorder may account for upwards of 10% of hereditary deafness. Previous genetic linkage studies localized the gene to a broad interval on human chromosome 7q22–31.1. Using a positional cloning strategy, we have identified the gene (PDS) mutated in Pendred syndrome and found three apparently deleterious mutations, each segregating with the disease in the respective families in which they occur. PDS produces a transcript of approximately 5 kb that was found to be expressed at significant levels only in the thyroid. The predicted protein, pendrin, is closely related to a number of known sulphate transporters. These studies provide compelling evidence that defects in pendrin cause Pendred syndrome thereby launching a new area of investigation into thyroid physiology, the pathogenesis of congenital deafness and the role of altered sulphate transport in human disease.