Mutation of BSND causes Bartter syndrome with sensorineural deafness and kidney failure

Antenatal Bartter syndrome (aBS) comprises a heterogeneous group of autosom al recessive salt-losing nephropathies'. identification of three genes that code for renal transporters and channels as responsible for aBS(2-7) has r esulted in new insights into renal salt handling, diuretic action and blood -pressure regulations. A gene locus of a fourth variant of aBS called BSND, which in contrast to the other forms is associated with sensorineural deaf ness (SND) and renal failure, has been mapped to chromosome 1p(9). We repor t here the identification by positional cloning, in a region not covered by the human genome sequencing projects, of a new gene, BSND, as the cause of BSND. We examined ten families with BSND and detected seven different muta tions in BSND that probably result in loss of function. In accordance with the phenotype, BSND is expressed in the thin limb and the thick ascending l imb of the loop of Henle in the kidney and in the dark cells of the inner e ar. The gene encodes a hitherto unknown protein with two putative transmemb rane a-helices and thus might function as a regulator for ion-transport pro teins involved in aBS, or else as a new transporter or channel itself.