Severe to profound sensorineural hearing loss is identified in about 1 in 500-1000 (4, 5) newborns, and at least half of these cases are due to genetic causes (6). Most of the genetic causes are nonsyndromic and autosomal recessive, meaning that there are no physical features and often no family history that can aid in determining the cause of hearing loss in a young child. Moreover, there are syndromic causes such as Usher syndrome and Pendred syndrome which have important implications later in life but which are difficult to diagnose clinically in the first few years. A common environmental cause of progressive childhood hearing loss, congenital CMV infection, may be missed at newborn screening and is difficult to diagnose after the first few months of life because of post-natal exposure. In addition to congenital hearing loss, hereditary progressive hearing loss often starts in early childhood. Accurate diagnosis can provide medical guidance to health care professionals and families, and identification of causal genes also allows researchers to determine the molecular pathways important for development and maintenance of hearing. Current molecular diagnostic methods, even those which are based on Next Generation sequencing methods, are limited to the sequencing of known genes causing deafness; for example, the University of Iowa is be offering sequencing of 66 genes that cause deafness. This covers just over half of the known loci for hearing loss, however. An additional 56 loci have been identified containing genes causing recessive or dominant nonsyndromic hearing loss, but the genes in these regions have not been determined, and it is likely that there are additional loci that have not yet been identified. Exome sequencing has the advantage of covering all genes for about the same sequencing cost as targeted sequencing, but additional research support is needed for the bioinformatic analysis to identify and verify new genes.
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