Function and Expression Pattern of Nonsyndromic Deafness Genes

Abstract

Hearing loss is the most common sensory disorder, present in 1 of every 500 newborns. To date, 46 genes have been identified that cause nonsyndromic hearing loss, making it an extremely heterogeneous trait. This review provides a comprehensive overview of the inner ear function and expression pattern of these genes. In general, they are involved in hair bundle morphogenesis, form constituents of the extracellular matrix, play a role in cochlear ion homeostasis or serve as transcription factors. During the past few years, our knowledge of genes involved in hair bundle morphogenesis has increased substantially. We give an up-to-date overview of both the nonsyndromic and Usher syndrome genes involved in this process, highlighting proteins that interact to form macromolecular complexes. For every gene, we also summarize its expression pattern and impact on hearing at the functional level. Gene-specific cochlear expression is summarized in a unique table by structure/cell type and is illustrated on a cochlear cross-section, which is available online via the Hereditary Hearing Loss Homepage. This review should provide auditory scientists the most relevant information for all identified nonsyndromic deafness genes.

Development of the stria vascularis and potassium regulation in the human fetal cochlea: Insights into hereditary sensorineural hearing loss

“…Depending on the studied population, 20–50% of all recessive nonsyndromic SNHL cases can be attributed to a mutation in GJB2 (Hilgert et al, 2009a; Linden Phillips et al, 2013). For a comprehensive overview of other affected genes, we refer to recent reviews (Hilgert et al, 2009b; Angeli et al, 2012; Shearer and Smith, 2012; Smith et al, 2014 2014; Stelma and Bhutta, 2014). …”

A deleterious mutation in the LOXHD1 gene causes autosomal recessive hearing loss in Ashkenazi Jews

“…Heretofore, over 60 loci for autosomal recessive NSHL (ARNSHL) are known, and 35 of the corresponding genes have been identified (http://hereditaryhearingloss.org). The discovery of disease causing mutations in these genes and those causing other form of genetic NSHL has allowed functional analysis, thus providing insights into the complex structure of the inner ear and the mechanism of hearing, enabling a pathophysiology based classification [Hilgert et al, 2009].…”

Potential Uses and Inherent Challenges of Using Genome-Scale Sequencing to Augment Current Newborn Screening

“…Hearing loss is the most common birth defect and the most prevalent sensorineural disorder in developed countries (Hilgert et al 2009). One of every 500 newborns has bilateral permanent sensorineural hearing loss that is greater or equal to a 40 decibel loss.…”