The Pendred syndrome gene encodes a chloride-iodide transport protein

Pendred syndrome is the most common form of syndromic deafness and characte rized by congenital sensorineural hearing loss and goitre(1-3). This disord er was mapped to chromosome 7 and the gene causing Pendred syndrome (PDS) w as subsequently identified by positional cloning(4-6). PDS encodes a putati ve transmembrane protein designated pendrin. Pendrin is closely related to a family of sulfate transport proteins that includes the rat sulfate-anion transporter(7) (encoded by Sat-1; 29% amino acid sequence identity), the hu man diastrophic dysplasia sulfate transporter(8) (encoded by DTD; 32%) and the human sulfate transporter 'downregulated in adenoma'(9,10) (encoded by DRA; 45%), On the basis of this homology and the presence of a slightly mod ified sulfate-transporter signature sequence comprising its putative second transmembrane domain(6-9), pendrin has been proposed to function as a sulf ate transporter. We were unable to detect evidence of sulfate transport fol lowing the expression of pendrin in Xenopus laevis oocytes by microinjectio n of PDS cRNA or in Sf9 cells following infection with PDS-recombinant bacu lovirus. The rates of transport for iodide and chloride were significantly increased following the expression of pendrin in both cell systems. Our res ults demonstrate that pendrin functions as a transporter of chloride and io dide, but not sulfate, and may provide insight into thyroid physiology and the pathophysiology of Pendred syndrome.