Asunto(s)
Síndrome Branquio Oto Renal/genética , Cromosomas Humanos Par 14/genética , Predisposición Genética a la Enfermedad/genética , Síndrome Branquio Oto Renal/patología , Mapeo Cromosómico , ADN/genética , Salud de la Familia , Femenino , Genoma Humano , Haplotipos/genética , Humanos , Escala de Lod , Masculino , Repeticiones de Microsatélite , LinajeRESUMEN
Antenatal Bartter syndrome (aBS) comprises a heterogeneous group of autosomal recessive salt-losing nephropathies. Identification of three genes that code for renal transporters and channels as responsible for aBS has resulted in new insights into renal salt handling, diuretic action and blood-pressure regulation. A gene locus of a fourth variant of aBS called BSND, which in contrast to the other forms is associated with sensorineural deafness (SND) and renal failure, has been mapped to chromosome 1p. We report 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 mutations 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 limb of the loop of Henle in the kidney and in the dark cells of the inner ear. The gene encodes a hitherto unknown protein with two putative transmembrane alpha-helices and thus might function as a regulator for ion-transport proteins involved in aBS, or else as a new transporter or channel itself.