Objectives: Mutations in the GJB2 gene have been of particular interest as it is the most common causative gene for congenital deafness in all populations. Detailed audiological features, including genotype-phenotype correlations, have been well documented. However, in spite of abundant gene as well as protein expression in the vestibular end organs, neither vestibular symptoms nor vestibular functions have yet been elucidated. In the present study, vestibular functions were evaluated in patients diagnosed with GJB2-related deafness. Subjects and Methods: Vestibular functions were evaluated by caloric test and cervical vestibular evoked myogenic potential (cVEMP) testing in 24 patients with biallelic GJB2 mutations. Results and Discussion: Twenty-one of 23 patients (91.3%) had normal caloric responses and significantly lower cVEMP amplitudes than the control subjects. In the patients who were able to undergo vestibular testing, the mostly normal reactions to caloric testing indicated that the lateral semicircular canal was intact. However, the majority of GJB2 patients showed low cVEMP reactions, indicating a saccular defect.

1.
Abe S, Usami S, Shinkawa, H, Kelley PM, Kimberling WJ: Prevalent connexin 26 gene (GJB2) mutations in Japanese. J Med Genet 2000;37:41-43.
2.
Ahmad S, Chen S, Sun J, Lin X: Connexins 26 and 30 are co-assembled to form gap junctions in the cochlea of mice. Biochem Biophys Res Commun 2003;307:362-368.
3.
Azaiez H, Chamberlin GP, Fischer SM, Welp CL, Prasad SD, Taggart RT, del Castillo I, Van Camp G, Smith RJ: GJB2: the spectrum of deafness-causing allele variants and their phenotype. Hum Mutat 2004;24:305-311.
4.
Burnham JA, Stirling CE: Quantitative localization of Na-K pump sites in the frog sacculus. J Neurocytol 1984;13:617-638.
5.
Bruzzone R, White TW, Paul DL: Connections with connexins: the molecular basis of direct intercellular signaling. Eur J Biochem 1996;238:1-27.
6.
Chan DK, Chang KW: GJB2-associated hearing loss: systematic review of worldwide prevalence, genotype, and auditory phenotype. Laryngoscope 2014;124:E34-E53.
7.
Cohen-Salmon M, Ott T, Michel V, Hardelin JP, Perfettini I, Eybalin M, Wu T, Marcus DC, Wangemann P, Willecke K, Petit C: Targeted ablation of connexin 26 in the inner ear epithelial gap junction network causes hearing impairment and cell death. Curr Biol 2002;12:1106-1111.
8.
Colebatch JG, Halmagyi GM, Skuse NF: Myogenic potentials generated by a click-evoked vestibulocollic reflex. J Neurol Neurosurg Psychiatry 1994;57:190-197.
9.
Dai P, Yu F, Han B, Liu X, Wang G, Li Q, Yuan Y, Liu X, Huang D, Kang D, Zhang X, Yuan H, Yao K, Hao J, He J, He Y, Wang Y, Ye Q, Yu Y, Lin H, Liu L, Deng W, Zhu X, You Y, Cui J, Hou N, Xu X, Zhang J, Tang L, Song R, Lin Y, Sun S, Zhang R, Wu H, Ma Y, Zhu S, Wu BL, Han D, Wong LJ: GJB2 mutation spectrum in 2,063 Chinese patients with nonsyndromic hearing impairment. J Transl Med 2009;14:7-26.
10.
Forge A, Becker D, Casalotti S, Edwards J, Marziano N, Nevill G: Gap junctions in the inner ear: comparison of distribution patterns in different vertebrates and assessment of connexin composition in mammals. J Comp Neurol 2003;467:207-231.
11.
Jun AI, McGuirt WT, Hinojosa R, Green GE, Fischel-Ghodsian N, Smith RJ: Temporal bone histopathology in connexin 26-related hearing loss. Laryngoscope 2000;110:269-275.
12.
Kasai M, Hayashi C, Iizuka T, Inoshita A, Kamiya K, Okada H, Nakajima Y, Kaga K, Ikeda K: Vestibular function of patients with profound deafness related to GJB2 mutation. Acta Otolaryngol 2010;130:990-995.
13.
Kikuchi T, Adams JC, Paul DL, Kimura RS: Gap junction systems in the rat vestibular labyrinth: immunohistochemical and ultrastructural analysis. Acta Otolaryngol 1994;114:520-528.
14.
Kikuchi T, Kimura RS, Paul DL, Adams JC: Gap junctions in the rat cochlea: immunohistochemical and ultrastructural analysis. Anat Embryol (Berl) 1995;191:101-118.
15.
Kimura RS: Distribution, structure, and function of dark cells in the vestibular labyrinth. Ann Otol Rhinol Laryngol 1969;78:542-561.
16.
Kudo T, Kure S, Ikeda K, Xia AP, Katori Y, Suzuki M, Kojima K, Ichinohe A, Suzuki Y, Aoki Y, Kobayashi T, Matsubara Y: Transgenic expression of a dominant-negative connexin 26 causes degeneration of the organ of Corti and non-syndromic deafness. Hum Mol Genet 2003;12:995-1004.
17.
Marcus DC, Shen Z: Slowly activating, voltage-dependent K conductance is apical pathway for K secretion in vestibular dark cells. Am J Physiol 1994;267:857-864.
18.
Marcus DC, Shipley AM: Potassium secretion by vestibular dark cell epithelium demonstrated by vibrating probe. Biophys J 1994;66:1939-1942.
19.
Martínez AD, Acuña R, Figueroa V, Maripillan J, Nicholson B: Gap-junction channels dysfunction in deafness and hearing loss. Antioxid Redox Signal 2009;11:309-322.
20.
Masuda M, Usami S, Yamazaki K, Takumi Y, Shinkawa H, Kurashima K, Kunihiro T, Kanzaki J: Connexin 26 distribution in gap junctions between melanocytes in the human vestibular dark cell area. Anat Rec 2001;262:137-146.
21.
Minami SB, Mutai H, Nakano A, Arimoto Y, Taiji H, Morimoto N, Sakata H, Adachi N, Masuda S, Sakamoto H, Yoshida H, Tanaka F, Morita N, Sugiuchi T, Kaga K, Matsunaga T: GJB2-associated hearing loss undetected by hearing screening of newborns. Gene 2013;532:41-45.
22.
Morton NE: Genetic epidemiology of hearing impairment. Ann NY Acad Sci 1991;630:16-31.
23.
Qu Y, Tang W, Dahlke I, Ding D, Salvi R, Söhl G, Willecke K, Chen P, Lin X: Analysis of connexin subunits required for the survival of vestibular hair cells. J Comp Neurol 2007;504:499-507.
24.
Sellick PM, Johnstone BM: The electrophysiology of the saccule. Pflugers Arch 1972;336:28-34.
25.
Shojaku H, Takemori S, Kobayashi K, Watanabe Y: Clinical usefulness of glycerol vestibular-evoked myogenic potentials: preliminary report. Acta Otolaryngol Suppl 2001;545:65-68.
26.
Snoeckx RL, Huygen PL, Feldmann D, Marlin S, Denoyelle F, Waligora J, Mueller-Malesinska M, Pollak A, Ploski R, Murgia A, Orzan E, Castorina P, Ambrosetti U, Nowakowska-Szyrwinska E, Bal J, Wiszniewski W, Janecke AR, Nekahm-Heis D, Seeman P, Bendova O, Kenna MA, Frangulov A, Rehm HL, Tekin M, Incesulu A, Dahl HH, du Sart D, Jenkins L, Lucas D, Bitner-Glindzicz M, et al: GJB2 mutations and degree of hearing loss: a multicenter study. Am J Hum Genet 2005;77:945-957.
27.
Steel KP, Kros CJ: A genetic approach to understanding auditory function. Nat Genet 2001;27:143-149.
28.
Teubner B, Michel V, Pesch J, Lautermann J, Cohen-Salmon M, Söhl G, Jahnke K, Winterhager E, Herberhold C, Hardelin JP, Petit C, Willecke K: Connexin 30 (Gjb6) deficiency causes severe hearing impairment and lack of endocochlear potential. Hum Mol Genet 2003;12:13-21.
29.
Todt I, Hennies HC, Basta D, Ernst A: Vestibular dysfunction of patients with mutations of connexin 26. Neuroreport 2005;16:1179-1181.
30.
Tsukada K, Nishio S, Usami S; Deafness Gene Study Consortium: A large cohort study of GJB2 mutations in Japanese hearing loss patients. Clin Genet 2010;78:464-470.
31.
Wangemann P: Comparison of ion transport mechanisms between vestibular dark cells and strial marginal cells. Hear Res 1995;90:149-157.
32.
Xu J, Nicholson BJ: The role of connexins in ear and skin physiology - functional insights from disease-associated mutations. Biochim Biophys Acta 2013;1828:167-178.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.