title: A novel missense variant in PRKCB segregates low-frequency hearing loss in an autosomal dominant family with Meniere's disease.
abstract: Meniere's Disease (MD) is a complex disorder associated with an accumulation of endolymph in the membranous labyrinth in the inner ear. It is characterized by recurrent attacks of spontaneous vertigo associated with sensorineural hearing loss (SNHL) and tinnitus. The SNHL usually starts at low and medium frequencies with a variable progression to high frequencies. We identified a novel missense variant in the PRKCB gene in a Spanish family with MD segregating low-to-middle frequency SNHL. Confocal imaging showed strong PKCB II protein labelling in non-sensory cells, the tectal cells and inner border cells of the rat organ of Corti with a tonotopic expression gradient. The PKCB II signal was more pronounced in the apical turn of the cochlea when compared with the middle and basal turns. It was also much higher in cochlear tissue than in vestibular tissue. Taken together, our findings identify PRKCB gene as a novel candidate gene for familial MD and its expression gradient in supporting cells of the organ of Corti deserves attention, given the role of supporting cells in K+recycling within the endolymph, and its apical turn location may explain the onset of hearing loss at low frequencies in MD.
authors.affiliation: Otology & Neurotology Group CTS495, Department of Genomic Medicine, GENYO - Centre for Genomics and Oncological Research - Pfizer/University of Granada/Junta de Andalucía, PTS, Granada 18016, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Martín-Sierra
authors.affiliation: Otology & Neurotology Group CTS495, Department of Genomic Medicine, GENYO - Centre for Genomics and Oncological Research - Pfizer/University of Granada/Junta de Andalucía, PTS, Granada 18016, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Requena
authors.affiliation: Otology & Neurotology Group CTS495, Department of Genomic Medicine, GENYO - Centre for Genomics and Oncological Research - Pfizer/University of Granada/Junta de Andalucía, PTS, Granada 18016, Spain.
authors.forename: Lidia
authors.initials: L
authors.lastname: Frejo
authors.affiliation: Dept. of Anatomy and Cell Biology, Univ. of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Price
authors.affiliation: Otology & Neurotology Group CTS495, Department of Genomic Medicine, GENYO - Centre for Genomics and Oncological Research - Pfizer/University of Granada/Junta de Andalucía, PTS, Granada 18016, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Gallego-Martinez
authors.affiliation: Department of Otolaryngology, Hospital Universitario Salamanca 37007, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Batuecas-Caletrio
authors.affiliation: Division of Otoneurology, Department of Otorhinolaryngology, Complexo Hospitalario Universitario, Santiago de Compostela 15706, Spain.
authors.forename: Sofía
authors.initials: S
authors.lastname: Santos-Pérez
authors.affiliation: Division of Otoneurology, Department of Otorhinolaryngology, Complexo Hospitalario Universitario, Santiago de Compostela 15706, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Soto-Varela
authors.affiliation: Dept. of Anatomy and Cell Biology, Univ. of Illinois at Chicago, Chicago, IL 60612, USA.|Dept. of Otolaryngology-Head and Neck Surgery, Univ. of Illinois at Chicago, Chicago IL 60612, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Lysakowski
authors.affiliation: Otology & Neurotology Group CTS495, Department of Genomic Medicine, GENYO - Centre for Genomics and Oncological Research - Pfizer/University of Granada/Junta de Andalucía, PTS, Granada 18016, Spain antonio.lopezescamez@genyo.es.|Department of Otolaryngology, Instituto de Investigación Biosanitaria ibs.GRANADA, Complejo Hospitalario Universidad de Granada (CHUGRA) Granada 18016, Spain.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Lopez-Escamez
mesh_terms: D000328:Adult; D000818:Animals; D007758:Ear, Inner / Q000473:pathology; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008575:Meniere Disease / Q000235:genetics* / Q000503:physiopathology; D020125:Mutation, Missense / Q000235:genetics*; D009925:Organ of Corti / Q000473:pathology; D010375:Pedigree; D064546:Protein Kinase C beta / Q000235:genetics*; D051381:Rats; D014012:Tinnitus / Q000235:genetics / Q000503:physiopathology
chemical_list: C579054:PRKCB protein, human; D064546:Protein Kinase C beta