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, Fahlke Christoph
Section on Human Genetics, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Rockville, MD 20850, USA.
Am J Hum Genet. 2009 Aug;85(2):273-80. doi: 10.1016/j.ajhg.2009.07.003. Epub 2009 Jul 30.
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.
BSND基因编码barttin，它是肾脏和内耳氯离子通道的一个辅助亚基。迄今为止，所有已发现的BSND基因突变均会导致IV型巴特综合征，其特征为显著的肾脏异常和耳聋。我们在四个家系中鉴定出一个BSND基因突变（p.I12T），这些家系中分离出与1号染色体1p32.3上4.04厘摩区间连锁的非综合征性耳聋。p.I12T的功能后果不同于导致IV型巴特综合征肾衰竭和耳聋的BSND基因突变。p.I12T不影响氯离子通道功能，仅在细胞内运输过程中干扰barttin的伴侣功能。本研究提供了功能数据，表明BSND的一个低表达等位基因是明显非综合征性耳聋的病因。我们证明，具有不同功能后果的BSND基因突变是综合征性或非综合征性耳聋的基础。
