Nature Genetics
21, 363 - 369 (1999)
doi:10.1038/7693
A mutation in OTOF, encoding otoferlin, a FER-1-like protein,
causes DFNB9, a nonsyndromic form of deafnessShin'ichiro Yasunaga1, 4, M'hamed Grati1, 4, Martine Cohen-Salmon1, Aziz El-Amraoui1, Mirna Mustapha1, 2, Nabiha Salem2, Elie El-Zir3, Jacques Loiselet2
& Christine Petit11
Unité de Génétique des Déficits
Sensoriels, CNRS URA 1968, Institut Pasteur, 25 rue du Dr Roux,
75724 Paris Cedex 15, France. 2
Laboratoire de Biochimie, Faculté de Médecine,
Université Saint-Joseph, Beyrouth, Lebanon. 3
Clinique d'Audiologie, Hôpital du Sacré-Coeur,
POB 116, Baabda, Brazilia, Lebanon. 4
These authors contributed equally to this work.
Correspondence should be addressed to Christine Petit cpetit@pasteur.frUsing 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.
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