Korean J Otorhinolaryngol-Head Neck Surg.  2014 Jan;57(1):1-6. 10.3342/kjorl-hns.2014.57.1.1.

Molecular Genetic Diagnosis of Deafness: Current and Future

• Oh SH
• Choi BY

• KMID: 1922194
• DOI: http://doi.org/10.3342/kjorl-hns.2014.57.1.1

Abstract

Advances in molecular biology and molecular genetic technologies have revealed extreme etiologic heterogeneity of genetic hearing loss. Genes known to contribute to deafness have been reported to be involved with a variety of function and structures in the cochlea of the inner ear. Genetic alteration in deafness genes manifests hearing loss either in syndromic or in nonsyndromic forms, albeit much more frequently in latter forms. Molecular genetic diagnosis in this nonsyndromic hearing loss is challenging in majority of cases. GJB2 is the most frequent etiology of severe to profound nonsyndromic hearing loss in most of the ethnic backgrounds. When no potentially pathogenic GJB2 mutation is detected, characteristic audiogram profiles and radiologic markers help us to select next candidate deafness genes. Mutations in SLC26A4 and POU3F4 causes enlarged vestibular aqueduct and incomplete partition type III anomaly, respectively. TECTA, TMPRSS3, WFS1, COCH, KCNQ4 and DIAPH1 give rise to a characteristic audiologic configuration, if mutated. This phenotype-driven candidate gene approach has been successful not infrequently. With the advent of next generation sequencing technologies, molecular genetic diagnosis of hearing impaired subjects even without any characteristic markers is being widely tried. Targeted resequencing of known deafness genes appears to be effective in as high as 50-60% in making molecular genetic diagnosis at least for multiplex families where there are two or more affected hearing impaired subjects. Whole exome sequencing has been successful in revealing molecular genetic etiology anecdotally. More sophisticated pipeline and platform for revealing pathogenicity of detected variants both genetically and biologically is necessary to incorporate the advent of cutting edge sequencing technologies to the big step toward a personalized rehabilitation for hearing impaired subjects.

Keyword

Deafness; Genes; Next generation sequencing; Phenotype-driven

MeSH Terms

Cochlea
Deafness*
Diagnosis*
Ear, Inner
Exome
Hearing
Hearing Loss
Humans
Molecular Biology*
Population Characteristics
Rehabilitation
Vestibular Aqueduct
Virulence