PubMed 20832469

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNQ4 , Kv7.4

Title: Pathogenic effects of a novel mutation (c.664_681del) in KCNQ4 channels associated with auditory pathology.

Authors: Jeong-In Baek, Hong-Joon Park, Kyungjoon Park, Su-Jin Choi, Kyu-Yup Lee, Jee Hyun Yi, Thomas B Friedman, Dennis Drayna, Ki Soon Shin, Un-Kyung Kim

Journal, date & volume: Biochim. Biophys. Acta, 2011 Apr , 1812, 536-43

PubMed link:

Hearing loss is a common communication disorder caused by various environmental and genetic factors. Hereditary hearing loss is very heterogeneous, and most of such cases involve sensorineural defects in the auditory pathway. There are currently 57 known autosomal dominant non-syndromic hearing loss (DFNA) loci, and the causative genes have been identified at 22 of these loci. In the present study, we performed a genome-wide linkage analysis in a Korean family segregating autosomal dominant hearing loss. We observed linkage on chromosome 1p34, and at this locus, we detected a novel mutation consisting of an 18 nucleotide deletion in exon 4 of the KCNQ4 gene, which encodes a voltage-gated potassium channel. We carried out a functional in vitro study to analyze the effects of this mutation (c.664_681del) along with two previously described KCNQ4 mutations, p.W276S and p.G285C. Although the c.664_681del mutation is located in the intercellular loop and the two previously described mutations, p.W276S and p.G285C, are located in the pore region, all mutants inhibit normal channel function by a dominant negative effect. Our analysis indicates that the intercellular loop is as significant as the pore region as a potential site of pathogenic effects on KCNQ4 channel function.