In addition, there are three non-syndromic X-linked genes known to date (, accessed February 24, 2014). Approximately 133 autosomal non-syndromic loci (55 dominant and 78 recessive) have been mapped, and within these, 78 genes are causally implicated in non-syndromic hearing loss: 30 for dominant and 48 for recessive hearing loss. There is considerable genetic heterogeneity underlying SNHL. Hereditary sensorineural hearing loss (SNHL) is a highly prevalent disorder in humans, affecting 1 in 500 newborns. Our study also demonstrates the challenges of exome sequencing and genome-wide CNV mapping for direct clinical application, and illustrates the need for functional and clinical follow-up as well as curated open-access databases. We conclude that many known as well as novel loci and distinct types of mutations not typically tested in clinical settings can contribute to the etiology of hearing loss. Additionally, a novel region on chromosome 16 containing part of the PDXDC1 gene was found to be frequently deleted in hearing loss patients (OR = 3.91, 95% CI: 1.62-9.40, p = 1.45 × 10 -7). GJB6, OTOA, and STRC, encoding connexin 30, otoancorin, and stereocilin, respectively), supporting CNV contributions to hearing loss phenotypes. High-resolution genome-wide CNV analysis of 150 cases and 157 controls revealed deletions in genes known to be involved in hearing (e.g. MYH7B encodes a Type II myosin, consistent with a role for cytoskeletal proteins in hearing. ResultsĪnalysis of three distinct families revealed several candidate loci in two families and a single strong candidate gene, MYH7B, for hearing loss in one family. To identify loci associated with predominantly non-syndromic sensorineural hearing loss, we performed exome sequencing of families and of single probands, as well as copy number variation (CNV) mapping in a case–control cohort. The genetic diversity of loci and mutations underlying hereditary hearing loss is an active area of investigation.