LINKAGE OF INFANTILE BARTTER-SYNDROME WITH SENSORINEURAL DEAFNESS TO CHROMOSOME 1P

Bartter syndrome (BS) is a family of disorders manifested by hypokalem ic hypochloremic metabolic alkalosis with normotensive hyperreninemic hyperaldosteronism. We evaluated a unique, inbred Bedouin kindred in w hich sensorineural deafness (SND) cosegregates with an infantile varia nt of the BS phenotype. Using a DNA-pooling strategy, we screened the human genome and successfully demonstrated linkage of this unique synd rome to chromosome 1p31. The genes for two kidney-specific chloride ch annels and a sodium/hydrogen antiporter, located near this region, wer e excluded as candidate genes. Although the search for the disease-cau sing gene in this family continues, this linkage further demonstrates the genetic heterogeneity of BS. In addition, the cosegregation of the se phenotypes allows us to postulate that a single genetic alteration may be responsible for the SND and the BS phenotype. The identificatio n and characterization of this gene would lead to a better understandi ng of the normal physiology of the kidney and the inner ear.