Molecular Diagnosis of Deafness by Genetic Testing

Abstract

One of the remarkable aspects associated with the identification of genes involved in hearing is that clinicians can sometimes make a molecular diagnosis by genetic testing. Such diagnoses are highly accurate and result in a considerable improvement in the predictability of hearing loss severity and associated abnormalities, the selection of appropriate habilitation options, and genetic counseling. GJB2 is currently recognized as the most prevalent gene responsible for congenital hearing loss. SLC26A4 is responsible for both Pendred syndrome and non-syndromic hearing loss associated with an enlarged vestibular aqueduct (EVA) and has also been demonstrated to be commonly responsible for recessive deafness. The 1555A→G mitochondrial mutation, known to be associated with a susceptibility to aminoglycoside antibiotics, has been identified as the most prevalent mitochondrial mutation. Our series of screening studies indicated that GJB2, SLC26A4, and the 1555A→G mitochondrial mutation were found to be the major causes of hearing loss in Japanese patients. In spite of progress in the identification of deafness genes, clinical application has lagged because of the genetic heterogeneity of deafness. Genetic screening based on recurrent mutations and ethnic databases of deafness genes using the Invader assay may be an appropriate strategy for the molecular diagnosis of deafness.