Yasunaga S, Grati M, Cohen-Salmon M, El-Amraoui A, Mustapha M, Salem N, El-Zir E, Loiselet J, Petit C
Unité de Génétique des Déficits Sensoriels, CNRS URA 1968, Institut Pasteur, Paris, France.
Nat Genet. 1999 Apr;21(4):363-9. doi: 10.1038/7693.
Using a candidate gene approach, we identified a novel human gene, OTOF, underlying an autosomal recessive, nonsyndromic prelingual deafness, DFNB9. The same nonsense mutation was detected in four unrelated affected families of Lebanese origin. OTOF is the second member of a mammalian gene family related to Caenorhabditis elegans fer-1. It encodes a predicted cytosolic protein (of 1,230 aa) with three C2 domains and a single carboxy-terminal transmembrane domain. The sequence homologies and predicted structure of otoferlin, the protein encoded by OTOF, suggest its involvement in vesicle membrane fusion. In the inner ear, the expression of the orthologous mouse gene, mainly in the sensory hair cells, indicates that such a role could apply to synaptic vesicles.
采用候选基因法，我们鉴定出一个新的人类基因OTOF，它是常染色体隐性非综合征性语前聋DFNB9的致病基因。在四个来自黎巴嫩的不相关患病家族中检测到相同的无义突变。OTOF是与秀丽隐杆线虫fer-1相关的哺乳动物基因家族的第二个成员。它编码一种预测的胞质蛋白（1230个氨基酸），具有三个C2结构域和一个单一的羧基末端跨膜结构域。OTOF编码的蛋白质otoferlin的序列同源性和预测结构表明它参与囊泡膜融合。在内耳中，直系同源小鼠基因主要在感觉毛细胞中表达，这表明这种作用可能适用于突触小泡。
