1. Molecular Basis of DFNB73: Mutations of BSND Can Cause Nonsyndromic Deafness or Bartter Syndrome.
- Author
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Riazuddin, Saima, Anwar, Saima, Fischer, Martin, Ahmed, Zubair M., Khan, Shahid Y., Janssen, Audrey G. H., Zafar, Ahmad U., Scholl, Ute, Husnain, Tayyab, Belyantseva, Inna A., Friedman, Penelope L., Riazuddin, Sheikh, Friedman, Thomas B., and Fahlke, Christoph
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BARTTER syndrome , *GENETICS of deafness , *KIDNEY abnormalities , *CHROMOSOMES , *CHLORIDE channels - Abstract
BSND encodes barttin, an accessory subunit of renal and inner ear chloride channels. To date, all mutations of BSND have been shown to cause Bartter syndrome type IV, characterized by significant renal abnormalities and deafness. We identified a BSND mutation (p.112T) in four kindreds segregating nonsyndromic deafness linked to a 4.04-cM interval on chromosome 1p32.3. The functional consequences of p.112T differ from BSND mutations that cause renal failure and deafness in Bartter syndrome type IV. p.112T leaves chloride channel function unaffected and only interferes with chaperone function of barttin in intracellular trafficking. This study provides functional data implicating a hypomorphic allele of BSND as a cause of apparent nonsyndromic deafness. We demonstrate that BSND mutations with different functional consequences are the basis for either syndromic or nonsyndromic deafness. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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