Open AccessSystematic Screening for KCTD12 Mutations Tinnitus
Author(s) -
Kleinjung Tobias,
Langguth Berthold,
Sand Philipp
Publication year - 2011
Publication title -
otolaryngology–head and neck surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.232
H-Index - 121
eISSN - 1097-6817
pISSN - 0194-5998
DOI - 10.1177/0194599811415823a307
Subject(s) - tinnitus , dominance (genetics) , genotype , allele , genetics , gabab receptor , phenotype , haplotype , biology , medicine , gene , receptor , audiology , gabaa receptor
Objective With regard to inhibition, GABAB receptors have been implicated in frequency‐dependent depression of transmitter release affecting synaptic plasticity. We speculated that genetic variation in potassium channel T1 domain‐containing 12 protein (KCTD12), a recently identified constituent of GABAB receptors, may predispose to over‐excitability as experienced by tinnitus subjects. Method A total of 81 white outpatients with a diagnosis of chronic tinnitus were systematically screened for mutations in the KCTD12 N‐terminal, cytoplasmic tetramerisation domain by direct sequencing. Results No novel variants were identified. We confirmed the presence of one synonymous substitution, rs34544607 (T178T), and one noncoding variant in the gene’s 3′UTR, rs41287030. When genotypes were grouped assuming dominance of the minor alleles, no significant genotype or compound genotype effects were observed on tinnitus severity by scores on the Tinnitus Questionnaire. Conclusion This is the first study to have addressed KCTD12 mutations in chronic tinnitus. Further investigations are invited in larger samples and in controls to assess a possible modulatory role of the above exonic variants on tinnitus susceptibility, or on related phenotypes.