Characterization of KCTD12/PFET1

The prevalence of severe to profound bilateral§congenital hearing loss is estimated at 1 in 1000§births, at least half of which can be attributed to a§genetic cause. As of 2005, mutations in at least 67§genes have been associated with hearing loss.§Discovery of these genes has revealed fundamental§processes within the ear, and enabled diagnosis and§implementation of genetic counseling in affected§patients. As a part of the continuing effort to study§genes important for hearing and deafness, this thesis§reports the identification and characterization of a§novel cochlear transcript with predominantly fetal§expression (PFET1/KCTD12) from the Morton fetal§cochlear cDNA library. KCTD12/Kctd12 is an§evolutionarily conserved intronless gene encoding a 6§kb transcript in human and three transcripts of§approximately 4, 4.5 and 6 kb in mouse. The protein,§pfetin, is predicted to contain a voltage-gated§potassium channel tetramerization (T1) domain.§Experimental data from tissue and cellular expression§profiling, and genetic and functional analysis§suggests KCTD12 and its orthologs playing a crucial§role in the developmental of the auditory sense organ.