Audioprofile-directed screening identifies novel mutations in KCNQ4 causing hearing loss at the DFNA2 locus

Abstract

PURPOSE: Gene identification in small families segregating autosomal dominant sensorineural hearing loss presents a significant challenge. To address this challenge, we have developed a machine learning-based software tool, AudioGene v2.0, to prioritize candidate genes for mutation screening based on audioprofiling. METHODS: We analyzed audiometric data from a cohort of American families with high-frequency autosomal dominant sensorineural hearing loss. Those families predicted to have a DFNA2 audioprofile by AudioGene v2.0 were screened for mutations in the KCNQ4 gene. RESULTS: Two novel missense mutations and a stop mutation were detected in three American families predicted to have DFNA2-..