title: Mutations in the gene encoding pejvakin, a newly identified protein of the afferent auditory pathway, cause DFNB59 auditory neuropathy.
abstract: 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.
authors.affiliation: Unité de Génétique des Déficits Sensoriels INSERM U587, Institut Pasteur, 25, rue du Docteur Roux, 75724 Paris Cedex 15, France.
authors.forename: Sedigheh
authors.initials: S
authors.lastname: Delmaghani
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: del Castillo
authors.forename: Vincent
authors.initials: V
authors.lastname: Michel
authors.forename: Michel
authors.initials: M
authors.lastname: Leibovici
authors.forename: Asadollah
authors.initials: A
authors.lastname: Aghaie
authors.forename: Uri
authors.initials: U
authors.lastname: Ron
authors.forename: Lut
authors.initials: L
authors.lastname: Van Laer
authors.forename: Nir
authors.initials: N
authors.lastname: Ben-Tal
authors.forename: Guy
authors.initials: G
authors.lastname: Van Camp
authors.forename: Dominique
authors.initials: D
authors.lastname: Weil
authors.forename: Francina
authors.initials: F
authors.lastname: Langa
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Paul
authors.initials: P
authors.lastname: Avan
authors.forename: Christine
authors.initials: C
authors.lastname: Petit
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001306:Auditory Pathways / Q000378:metabolism* / Q000473:pathology; D001483:Base Sequence; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D004247:DNA / Q000235:genetics; D007758:Ear, Inner / Q000378:metabolism / Q000473:pathology; D005260:Female; D005808:Genes, Recessive; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D000094524:Gasdermins
chemical_list: D004247:DNA; D009419:Nerve Tissue Proteins; C519847:PJVK protein, human; D000094524:Gasdermins