GENETICS OF HEARING LOSS

Salido E

Research Unit, Hospital Universitario de Canarias, Santa Cruz de tenerife, Spain

Hearing impairment is the most common sensory disorder, present in almost 1 of every 500 newborns. Deafness is also an extremely heterogeneous trait, with close to 50 genes implicated in nonsyndromic hearing loss. Considerable progress has been made over the past decade identifying the many genes associated with deafness. As a result of the identification of these deafness genes and the functional characterization of the proteins they encode, we have gained unprecedented insight into the molecular mechanisms of hearing in the peripheral auditory system. Indeed, the molecules involved in the development and function of the cochlea eluded characterization until recently owing to the scarcity of the principal cell types present. But the “reverse genetic” approach has circumvented this problem and succeeded in identifying proteins and deciphering some of the molecular complexes that operate in these cells. The mechanosensory device of the sensory hair cell, the hair bundle, has been the subject of recent advances in cochlea development, its operation as a mechanotransducer and how it processes sound. With the recent explosion of mouse models, the genetic approach is now revealing some of the principles underlying the development and physiology of the cochlea. Many of the key genes that are involved in the development and functioning of the auditory system have been elucidated with the help of mouse mutants.  A combination of genetic and physiological studies of mutant mice, together with the molecular analysis of protein networks of the stereocilia bundle in the inner ear, are identifying crucial elements of auditory function and providing deep insight into the underlying causes of hearing loss.

The most frequent genes implicated in autosomal recessive nonsyndromic hearing loss are GJB2, which is responsible for more than half of cases, followed by SLC26A4, MYO15A, OTOF, CDH23 and TMC1. None of the genes associated with autosomal dominant nonsyndromic hearing loss accounts for a majority of  cases, although mutations are somewhat more frequently reported in WFS1, KCNQ4, COCH and GJB2. Only a minority of these genes is currently included in genetic diagnostics, but the situation is likely to change as sequencing technology becomes more widely spread and affordable.