Characterization in cochlea of KCTD12/PFET1, an intronless gene with predominant fetal expression

Abstract

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. To date, 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, a novel cochlear transcript with predominantly fetal expression containing a single tetramerization domain (PFET1, HUGO-approved symbol KCTD]2) was identified from the Morton fetal cochlear cDNA library. KCTD12/Kctd]2 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. This thesis reports characterization of this novel human gene and its encoded protein pfetin in relation to its role in auditory function. Experimental data from tissue and cellular expression profiling, and genetic and functional analyses suggests KCTD12 and its orthologs playing a crucial role in the developmental of the auditory sense organ.