A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness

Using a candidate gene approach, we identified a novel human gene, OTOF, un derlying an autosomal recessive, nonsyndromic prelingual deafness, DFNB9. T he same nonsense mutation was detected in four unrelated affected families of Lebanese origin. OTOF is the second member of a mammalian gene family re lated to Caenorhabditis elegans fer-1. It encodes a predicted cytosolic pro tein (of 1,230 aa) with three C2 domains and a single carboxy-terminal tran smembrane domain. The sequence homologies and predicted structure of otofer lin, the protein encoded by OTOF, suggest its involvement in vesicle membra ne 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.