Nature Genetics 38, 770 - 778 (2006)
Published online: 25 June 2006; | doi:10.1038/ng1829
Mutations in the gene encoding pejvakin, a newly identified protein of the afferent auditory pathway, cause DFNB59 auditory neuropathySedigheh Delmaghani1, Francisco J del Castillo1, Vincent Michel1, Michel Leibovici1, Asadollah Aghaie1, Uri Ron2, Lut Van Laer3, Nir Ben-Tal2, Guy Van Camp3, Dominique Weil1, Francina Langa4, Mark Lathrop5, Paul Avan6 & Christine Petit11
Unité de Génétique des Déficits Sensoriels INSERM U587, Institut Pasteur, 25, rue du Docteur Roux, 75724
Paris
Cedex 15, France. 2
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel Aviv, Israel. 3
Department of Medical Genetics, University of Antwerp, Antwerp, Belgium. 4
Centre d'Ingénierie Génétique Murine, Institut Pasteur, Paris, France. 5
Centre National de Génotypage, Evry, France. 6
Laboratoire de Biophysique Sensorielle, Faculté de Médecine, Université d'Auvergne, Clermont-Ferrand, France.
Correspondence should be addressed to Christine Petit cpetit@pasteur.fr Auditory neuropathy is a particular type of hearing impairment in which neural transmission of the auditory signal is impaired, while cochlear outer hair cells remain functional. Here we report on DFNB59, a newly identified gene on chromosome 2q31.1–q31.3 mutated in four families segregating autosomal recessive auditory neuropathy. DFNB59 encodes pejvakin, a 352-residue protein. Pejvakin is a paralog of DFNA5, a protein of unknown function also involved in deafness. By immunohistofluorescence, pejvakin is detected in the cell bodies of neurons of the afferent auditory pathway. Furthermore, Dfnb59 knock-in mice, homozygous for the R183W variant identified in one DFNB59 family, show abnormal auditory brainstem responses indicative of neuronal dysfunction along the auditory pathway. Unlike previously described sensorineural deafness genes, all of which underlie cochlear cell pathologies, DFNB59 is the first human gene implicated in nonsyndromic deafness due to a neuronal defect.
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