Genomics of Hereditary Deafness

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講演要旨

Our ability to perceive sound is facilitated by the inner ear, an elaborate structure with six sensory organs, which includes the organ of Corti in the cochlea for hearing and the organs of the vestibular system for balance. The sensory organs contain epithelial hair cells, the sites of mechanotransduction that facilitate the transformation of mechanical forces into electrical signals. This extraordinary process allows humans to hear and enables communication, orientation and reaction to danger, and the ability to listen to music. With over 360 million people suffering from hearing loss worldwide, over 50% of these cases are predicted to be caused by inherited pathogenic variants. Hearing loss is genetically heterogeneous, with hundreds of genes involved. Determining the etiology of hearing loss is crucial for clinical management, determining the prognosis of hearing loss and other abnormalities and assessing the recurrence rate in family members. The use of isolated populations, such as those of the Middle East, has had a strong influence on the discovery of deafness genes worldwide. We applied targeted gene enrichment, along with massively parallel sequencing, of over 300 genes associated with deafness genes on unrelated families of Israeli Jewish and Palestinian Arab origin. We identified variants that are candidates for deafness in our patients. For unsolved families, a whole exome sequencing approach is being taken. Our epigenetic study of the mouse sensory epithelium is revealing regulatory genomic regions that may harbor genetic or epigenetic mechanisms responsible for as-yet-unsolved forms of human deafness. Cellular and mouse models for human deafness enables functional analysis to link variants to pathogenicity. Deciphering the genetic basis of hearing is leading to the elucidation of mechanisms underlying the pathophysiology of deafness, with potential development of therapeutic options.