Genetic Elucidation of Nonsyndromic Hearing Loss in the High-Throughput Sequencing Era

Abstract

Hereditary hearing loss is a classic genetically heterogeneous condition with nearly 100 nonsyndromic hearing loss genes currently described and many more awaiting discovery. Priorities in the field with potentially rapid clinical application are the identification of all genes involved in the biological mechanisms of hearing and understanding their coordinated molecular interplay for normal auditory and nervous system functioning. Much of this momentum has been hindered by the inherent complexities of the genetics underlying deafness, as well as constraints such as requirements of large families for successful positional cloning. Major technological advancements in the past decade have empowered high-throughput next-generation sequencing approaches that have already facilitated the recognition of over 30 genes since 2010 and shifted hurdles away from achieving economical and time-efficient data toward accurate variant prioritization. Progress in the field of molecular genetics has never occurred at such a remarkable pace or been at such an exciting crossroad for expedited identification of the genes involved in hearing loss.