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      Deep resequencing of the voltage-gated potassium channel subunit KCNE3 gene in chronic tinnitus

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      Behavioral and Brain Functions : BBF
      BioMed Central

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          Abstract

          Membrane-stabilizing drugs have long been used for the treatment of chronic tinnitus, suggesting an underlying disturbance of sensory excitability due to changes in ion conductance. The present study addresses the potassium channel subunit gene KCNE3 as a potential candidate for tinnitus susceptibility. 288 Caucasian outpatients with a diagnosis of chronic tinnitus were systematically screened for mutations in the KCNE3 open reading frame and in the adjacent region by direct sequencing. Allele frequencies were determined for 11 known variants of which two (F66F and R83H) were polymorphic but were not associated with the disorder. No novel variants were identified and only three carriers of R83H were noted. However, owing to a lack of power, our study can neither rule out effects of KCNE3 on the risk for developing chronic tinnitus, nor can it exclude a role in predicting the severity of tinnitus. More extensive investigations are invited, including tests for possible effects of variation in this ion channel protein on the response to treatment.

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          Most cited references32

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          The UCSC Genome Browser database: update 2010

          The University of California, Santa Cruz (UCSC) Genome Browser website (http://genome.ucsc.edu/) provides a large database of publicly available sequence and annotation data along with an integrated tool set for examining and comparing the genomes of organisms, aligning sequence to genomes, and displaying and sharing users’ own annotation data. As of September 2009, genomic sequence and a basic set of annotation ‘tracks’ are provided for 47 organisms, including 14 mammals, 10 non-mammal vertebrates, 3 invertebrate deuterostomes, 13 insects, 6 worms and a yeast. New data highlights this year include an updated human genome browser, a 44-species multiple sequence alignment track, improved variation and phenotype tracks and 16 new genome-wide ENCODE tracks. New features include drag-and-zoom navigation, a Wiki track for user-added annotations, new custom track formats for large datasets (bigBed and bigWig), a new multiple alignment output tool, links to variation and protein structure tools, in silico PCR utility enhancements, and improved track configuration tools.
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            A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome.

            The Jervell and Lange-Nielsen (JLN) syndrome (MIM 220400) is an inherited autosomal recessive disease characterized by a congenital bilateral deafness associated with a QT prolongation on the electrocardiogram, syncopal attacks due to ventricular arrhythmias and a high risk of sudden death. JLN syndrome is a rare disease, which seems to affect less than one percent of all deaf children. Linkage to chromosome 11p15.5 markers was found by analysing four consanguinous families. Recombinants allowed us to map the JLN gene between D11S922 and D11S4146, to a 6-cM interval where KVLQT1, a potassium channel gene causing Romano-Ward (RW) syndrome, the dominant form of long QT syndrome, has been previously localized. An homozygous deletion-insertion event (1244, -7 +8) in the C-terminal domain of this gene was detected in three affected children of two families. We found that KVLQT1 is expressed in the stria vascularis of mouse inner ear by in situ hybridization. Taken together, our data indicate that KVLQT1 is responsible for both JLN and RW syndromes and has a key role not only in the ventricular repolarization but also in normal hearing, probably via the control of endolymph homeostasis.
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              [The tinnitus questionnaire. A standard instrument for grading the degree of tinnitus. Results of a multicenter study with the tinnitus questionnaire].

              The clinical examination of patients with severe and chronic tinnitus must include associated psychological disturbances. The present paper describes traditional diagnostic methods of ENT practice as well as the Tinnitus Questionnaire (TQ) which has been evaluated in a number of studies. This instrument differentiates between emotional and cognitive distress, auditory perceptual difficulties and self-experienced intrusiveness produced by the tinnitus. The results of a German multicenter study are presented which show that the TQ can be used to demonstrate differences of tinnitus distress under different clinical conditions (e.g., ENT clinic vs psychosomatic clinic and in- vs out-patient care). The TQ can be employed for comparative studies in different tinnitus-related institutions and for the evaluation of the relative effects of different treatment approaches.
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                Author and article information

                Journal
                Behav Brain Funct
                Behavioral and Brain Functions : BBF
                BioMed Central
                1744-9081
                2011
                7 September 2011
                : 7
                : 39
                Affiliations
                [1 ]Department of Psychiatry, University of Regensburg Universitätsstr. 84, 93042 Regensburg, Germany
                [2 ]Department of Otorhinolaryngology, University of Regensburg Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany
                [3 ]Department of Otorhinolaryngology, University of Zurich, Frauenklinikstrasse 24, 8091 Zurich, Switzerland
                Article
                1744-9081-7-39
                10.1186/1744-9081-7-39
                3180252
                21899751
                b305fa9f-cf6d-4503-b96c-88af1ad0f77b
                Copyright ©2011 Sand et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 February 2011
                : 7 September 2011
                Categories
                Short Paper

                Neurology
                Neurology

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