PENDRED SYNDROME IS CAUSED BY MUTATIONS IN A PUTATIVE SULFATE TRANSPORTER GENE (PDS)

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 interva l on human chromosome 7q22-31.1. Using a positional cloning strategy, we have identified the gene (PDS) mutated in Pendred syndrome and foun d three apparently deleterious mutations, each segregating with the di sease in the respective families in which they occur. PDS produces a t ranscript of approximately 5 kb that was found to be expressed at sign ificant levels only in the thyroid. The predicted protein, pendrin, is closely related to a number of known sulphate transporters. These stu dies provide compelling evidence that defects in pendrin cause Pendred syndrome thereby launching a new area of investigation into thyroid p hysiology, the pathogenesis of congenital deafness and the role of alt ered sulphate transport in human disease.