Related Experiment Video
Updated: Jun 1, 2026
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Audioprofile-directed successful mutation analysis in a DFNA2/KCNQ4 (p.Leu274His) family
Anne-Martine R de Heer1, Margit Schraders, Jaap Oostrik
1Department of Otorhinolaryngology-Raboud University Nijmegen Medical Center, Clinical Neuroscience Donders Center for Brain, Cognition and Behavior, Nijmegen, The Netherlands.
Objectives:
We undertook to show that in a family with nonsyndromic autosomal dominant sensorineural hearing loss, genetic analysis can be successful when there is a match with a specific DFNA audioprofile. We also provide an update of relevant DFNA2/KCNQ4 audioprofiles and report the results of automatic audioprofile analysis using the Internet program AudioGene.
Methods:
Audiometric data and blood samples were obtained from the family W08-0384. Based on the audiograms of the affected participants, mutation analysis of KCNQ4 was started. Original audiometric threshold data were collected for all identified KCNQ4-related DFNA2 families. The Internet computer program AudioGene, recently developed for automatic audioprofile analysis, was accessed.
Results:
The family's audioprofile and the program AudioGene predicted the DFNA2/KCNQ4 locus. Mutation analysis of KCNQ4 revealed a c.821T>A (p.Leu274His) mutation of the KCNQ4 gene. This mutation has been previously identified in a Dutch family. Genetic analysis revealed a common haplotype in these two families over a region including the KCNQ4 gene.
Conclusions:
Familiarity with the audioprofiles of DFNA traits may lead to successful mutation analysis of the gene involved, even in a small family in which genetic linkage analysis is not an option. Alternatively, the specially developed program AudioGene can be accessed on the Internet to perform automatic audioprofile analysis of a family's (audiological) phenotype.
