Molecular Basis of DFNB73: Mutations of BSND
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- 作者：Saima Riazuddin ; Saima Anwar ; Martin Fischer ; Zubair M. Ahmed ; Shahid Y. Khan ; Audrey G.H. Janssen ; Ahmad U. Zafar ; Ute Scholl ; Tayyab Husnain ; Inna A. Belyantseva ; Penelope L. Friedman ; Sheikh Riazuddin ; Thomas B. Friedman ; Christoph Fahlke
- 刊名：The American Journal of Human Genetics
- 出版年：2009
- 出版时间：14 August 2009
- 年：2009
- 卷：85
- 期：2
- 页码：273-280
- 全文大小：1401 K
文摘
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.I12T) in four kindreds segregating nonsyndromic deafness linked to a 4.04-cM interval on chromosome 1p32.3. The functional consequences of p.I12T differ from BSND mutations that cause renal failure and deafness in Bartter syndrome type IV. p.I12T 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.