Molecular diagnosis of deafness: impact of gene identification

Recent progress in identifying genes responsible for hearing loss enables the ENT clinician to apply molecular diagnosis by genetic testing. This article focuses on three genes, which are prevalent and therefore commonly encountered in the clinic. GJB2 (connexin 26) is currently recognized as the most prevalent gene responsible for congenital hearing loss in many countries. A series of reports revealed that different combinations of GJB2 mutations exist in different ethnic populations, indicating that ethnic background should be considered when performing genetic testing. GJB2 mutations will be of particular interest in combination with universal infant hearing screening programs, because it has been shown that early identification of hearing loss and early intervention are crucial for language development. Progress in genetic analysis has changed the concept of diseases. The present review introduces the example of two historically distinct categories of disease, Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct, which are currently considered to be a continuum of diseases caused by the same gene, PDS. This review also emphasizes that some hearing impairment can be prevented. The 1555A-->G mitochondrial mutation, the most prevalent mitochondrial mutation found in the hearing-impaired population, was found in approximately 3% of the outpatients. The 1555A-->G mutation is known to be associated with a susceptibility to aminoglycoside antibiotics. There may be a considerably large high-risk population and to avoid possible side effects in this group, a rapid mass screening system and careful counseling are recommended.