An Examination of KCNE1 Mutations and Common Variants in Chronic Tinnitus

Genes

Philipp G. Sand¹  Alexander Luettich³  Tobias Kleinjung²  Goeran Hajak¹ 

[1] Department of Psychiatry, University of Regensburg, Universitaetsstr. 84, 93042 Regensburg, Germany; E-Mails:;Department of Otorhinolaryngology, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany; E-Mail:;Experimental and Clinical Neurosciences Graduate Program, University of Regensburg, Germany; E-Mail:

关键词: tinnitus;    KCNE1;    missense mutation;    hearing disorder;   

DOI  :  10.3390/genes1010023

来源: mdpi

【 摘 要 】

Chronic tinnitus is a highly prevalent and often incapacitating condition frequently associated with sensorineural hearing loss. While its etiology remains incompletely understood there is a growing awareness of genetic factors that predispose to, or aggravate chronic tinnitus. Candidate genes for the disorder include KCNE1, a potassium channel subunit gene that has been implicated in maturation defects of central vestibular neurons, in Menière's disease, and in noise-induced hearing loss. 201 Caucasian outpatients with a diagnosis of chronic tinnitus were systematically screened for mutations in the KCNE1 open reading frame and in the adjacent sequence by direct sequencing. Allele frequencies were determined for 46 known variants, plus two novel KCNE1 mutations. These comprised one missense substitution (V47I) in the highly conserved region encoding the KCNE1 transmembrane domain, and one rare variant in the gene's 3'UTR. When genotypes were grouped assuming dominance of the minor alleles, no significant genotype or compound genotype effects were observed on tinnitus severity. The newly identified V47I substitution argues in favor of an enlarged spectrum of mutations in hearing disorders. However, with regard to allele frequencies in healthy control populations from earlier studies, more common KCNE1 variants are unlikely to play a major role in chronic tinnitus. Further investigations are invited to address variation in additional channel subunits as possible risk factors in tinnitus.

【 授权许可】

CC BY   
© 2010 by the authors; licensee MDPI, Basel, Switzerland