Deafness gene discovery in the genomic era

Tal Elkan-Miller*, Karen B. Avraham

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


Hereditary deafness is a genetically heterogeneous disease, with wide variation in clinical symptoms displayed, including age of onset, frequencies affected, and changes in hearing threshold. As a result, there are some common and many more rare forms of deafness, each represented by mutations in different genes. The major challenge and goal in the field has been to identify the genes containing mutations leading to deafness, and to elucidate the auditory and vestibular pathways the proteins they encode are involved in. A remarkable amount of data has accumulated over the years to address the mechanisms associated with normal hearing and pathology of the inner ear. To date, there are 60 genes known to be involved in non-syndromic hearing loss (NSHL), and 34 genes known to be associated with 10 forms of syndromic hearing loss (SHL). Nevertheless, it is estimated that there are many more genes to be found implicated in human deafness. Furthermore, there are countless small families that remain unsolved with respect to the cause of their sensory loss. The difficulties of obtaining large pedigrees, the laborious process of genotyping, linkage analysis, positional cloning, and sequencing of dozens of genes in a critical region has hindered the process of further gene discovery. Clinically, this has limited carrier testing of deafness-causing mutations only to the most common ones, or to a specific mutation having been found previously found in the same ethnic population. Therefore the reality is that despite there being over 60 known genes, only one to four genes can be examined for each patient. Since the completion of the Human Genome Project (HGP) and the appearance of Next Generation Sequencing (NGS), or Massively Parallel Sequencing (MPS) and Deep Sequencing, technologies, rapid highthroughput identification of new deafness genes and mutations has been greatly streamlined. A single deep sequencing experiment can be completed within a few days and lead to the identification of new mutations. While the computational analysis and validation of variants still remains the bottleneck for finding new mutations, as more genes are discovered and bioinformatics tools developed, this process will become much easier. The application of genomic analysis for early clinical diagnosis of deafness will enable prediction of abnormal phenotypes that might arise later, improve rehabilitation of deaf children and simplify decisions for subsequent treatment. Identification of more genes involved in the auditory and vestibular pathways will help elucidate pathways and mechanisms of inner ear function. In this chapter we will review the advances deep sequencing is having on the discovery of new deafness genes and pathogenic mutations in these genes.

Original languageEnglish
Title of host publicationInner Ear Development and Hearing Loss
PublisherNova Science Publishers, Inc.
Number of pages16
ISBN (Print)9781624170119
StatePublished - Jan 2013


Dive into the research topics of 'Deafness gene discovery in the genomic era'. Together they form a unique fingerprint.

Cite this